rrm2 protein levels Search Results


94
Proteintech ihcwere
Ihcwere, supplied by Proteintech, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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ABclonal Biotechnology rrm2
A GSEA analysis comparing sotorasib, adavosertib, and combination groups to the control group, as well as comparing the combination group to sotorasib and adavosertib groups. B NES values of E2F targets and G2M checkpoint pathways in GSEA analysis, with pairwise comparisons among the four treatment groups. C Venn diagram of the top 20 genes in E2F targets pathway comparing the combination group to sotorasib group, adavosertib group and control group. D Venn diagram of the top 20 genes in G2M checkpoint pathway comparing the combination group to sotorasib group, adavosertib group and control group. E Flowchart illustrating the identification of <t>RRM2</t> transcription factors using TCGA LUAD and GSE31210 and GSE30219 datasets. F The correlation between MYBL2, CENPA, FOXM1, E2F1, ZNF367, and HMGA1 with RRM2 in RNA-seq data. G, H The correlation between MYBL2 and RRM2 in TCGA LUAD ( G ) and our RNA-seq ( H ). I The schematic diagram for two MYBL2 binding motifs on RRM2 promoter (FL) and related truncated (ST) and site-mutated promoter (S-mut) constructs. J Relative luciferase reporter activity of RRM2 promoter (−2000 ~ + 60) while co-transfected with MYBL2 expression plasmid for 48 h in H2122 and H23 cells. K Relative luciferase reporter activity of the truncated and site-mutated RRM2 promoters while co-transfected with MYBL2 expression plasmid for 48 h in H2122 cells. L The expression of MYBL2 and RRM2 proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h. M The expression of phosphorylation and total levels of ERK and AKT proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h.
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90
CEM Corporation shrna
A GSEA analysis comparing sotorasib, adavosertib, and combination groups to the control group, as well as comparing the combination group to sotorasib and adavosertib groups. B NES values of E2F targets and G2M checkpoint pathways in GSEA analysis, with pairwise comparisons among the four treatment groups. C Venn diagram of the top 20 genes in E2F targets pathway comparing the combination group to sotorasib group, adavosertib group and control group. D Venn diagram of the top 20 genes in G2M checkpoint pathway comparing the combination group to sotorasib group, adavosertib group and control group. E Flowchart illustrating the identification of <t>RRM2</t> transcription factors using TCGA LUAD and GSE31210 and GSE30219 datasets. F The correlation between MYBL2, CENPA, FOXM1, E2F1, ZNF367, and HMGA1 with RRM2 in RNA-seq data. G, H The correlation between MYBL2 and RRM2 in TCGA LUAD ( G ) and our RNA-seq ( H ). I The schematic diagram for two MYBL2 binding motifs on RRM2 promoter (FL) and related truncated (ST) and site-mutated promoter (S-mut) constructs. J Relative luciferase reporter activity of RRM2 promoter (−2000 ~ + 60) while co-transfected with MYBL2 expression plasmid for 48 h in H2122 and H23 cells. K Relative luciferase reporter activity of the truncated and site-mutated RRM2 promoters while co-transfected with MYBL2 expression plasmid for 48 h in H2122 cells. L The expression of MYBL2 and RRM2 proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h. M The expression of phosphorylation and total levels of ERK and AKT proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h.
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90
CEM Corporation ve-822
A GSEA analysis comparing sotorasib, adavosertib, and combination groups to the control group, as well as comparing the combination group to sotorasib and adavosertib groups. B NES values of E2F targets and G2M checkpoint pathways in GSEA analysis, with pairwise comparisons among the four treatment groups. C Venn diagram of the top 20 genes in E2F targets pathway comparing the combination group to sotorasib group, adavosertib group and control group. D Venn diagram of the top 20 genes in G2M checkpoint pathway comparing the combination group to sotorasib group, adavosertib group and control group. E Flowchart illustrating the identification of <t>RRM2</t> transcription factors using TCGA LUAD and GSE31210 and GSE30219 datasets. F The correlation between MYBL2, CENPA, FOXM1, E2F1, ZNF367, and HMGA1 with RRM2 in RNA-seq data. G, H The correlation between MYBL2 and RRM2 in TCGA LUAD ( G ) and our RNA-seq ( H ). I The schematic diagram for two MYBL2 binding motifs on RRM2 promoter (FL) and related truncated (ST) and site-mutated promoter (S-mut) constructs. J Relative luciferase reporter activity of RRM2 promoter (−2000 ~ + 60) while co-transfected with MYBL2 expression plasmid for 48 h in H2122 and H23 cells. K Relative luciferase reporter activity of the truncated and site-mutated RRM2 promoters while co-transfected with MYBL2 expression plasmid for 48 h in H2122 cells. L The expression of MYBL2 and RRM2 proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h. M The expression of phosphorylation and total levels of ERK and AKT proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h.
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96
Proteintech ki67
A H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days shown in tumor growth. n = 5 mice, with 10 tumors per group. B Percent survival in H2122 xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. Tumor volume exceeding 600 mm 3 is considered lethal. n = 10 tumors per group. C Waterfall plot analyses of changes in tumor volume at the end of treatment. n = 10 tumors per group. D Photograph of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. E Tumor mass of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. F Body weight of mice bearing H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 5 mice per group. G H&E staining, IHC staining, and TUNEL staining of xenografts tumors. Scale bar, 100 μm in the full image and 25 μm in the magnified image of the top right corner. For TUNEL staining, The blue fluorescence (DAPI) in tumor represented for tumor cells and red fluorescence (TUNEL, TMR red) represented for apoptosis tumor cells. Scale bar, 50 μm. H The staining expression of <t>Ki67,</t> MYBL2, RRM2, pH2AX and apoptosis index in xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. n = 9 per group. Expression is calculated using three slices per group, with three randomly selected regions per slice. I The correlation between MYBL2 and RRM2 IHC H score in xenografts tumors. n = 12. J Abstract. In KRAS-G12C mutant NSCLC, the combination of G12Ci and WEE1i synergistically suppresses the MYBL2-RRM2 axis. This suppression leads to a reduction in dNTPs, triggers DNA replication stress, and results in the accumulation of DNA damage, ultimately culminating in apoptosis. Data are mean ± SD of independent replicates.
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90
CEM Corporation protein levels in cem shrnarrm2 cells as determined by nlcms/ms
A H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days shown in tumor growth. n = 5 mice, with 10 tumors per group. B Percent survival in H2122 xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. Tumor volume exceeding 600 mm 3 is considered lethal. n = 10 tumors per group. C Waterfall plot analyses of changes in tumor volume at the end of treatment. n = 10 tumors per group. D Photograph of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. E Tumor mass of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. F Body weight of mice bearing H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 5 mice per group. G H&E staining, IHC staining, and TUNEL staining of xenografts tumors. Scale bar, 100 μm in the full image and 25 μm in the magnified image of the top right corner. For TUNEL staining, The blue fluorescence (DAPI) in tumor represented for tumor cells and red fluorescence (TUNEL, TMR red) represented for apoptosis tumor cells. Scale bar, 50 μm. H The staining expression of <t>Ki67,</t> MYBL2, RRM2, pH2AX and apoptosis index in xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. n = 9 per group. Expression is calculated using three slices per group, with three randomly selected regions per slice. I The correlation between MYBL2 and RRM2 IHC H score in xenografts tumors. n = 12. J Abstract. In KRAS-G12C mutant NSCLC, the combination of G12Ci and WEE1i synergistically suppresses the MYBL2-RRM2 axis. This suppression leads to a reduction in dNTPs, triggers DNA replication stress, and results in the accumulation of DNA damage, ultimately culminating in apoptosis. Data are mean ± SD of independent replicates.
Protein Levels In Cem Shrnarrm2 Cells As Determined By Nlcms/Ms, supplied by CEM Corporation, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/rrm2+protein+levels/protein+levels+in+cem+shrnarrm2+cells+as+determined+by+nlcms+ms/pmc05556071__41467_2017_221_MOESM1_ESM-19-104-142
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93
Proteintech mybl2
A GSEA analysis comparing sotorasib, adavosertib, and combination groups to the control group, as well as comparing the combination group to sotorasib and adavosertib groups. B NES values of E2F targets and G2M checkpoint pathways in GSEA analysis, with pairwise comparisons among the four treatment groups. C Venn diagram of the top 20 genes in E2F targets pathway comparing the combination group to sotorasib group, adavosertib group and control group. D Venn diagram of the top 20 genes in G2M checkpoint pathway comparing the combination group to sotorasib group, adavosertib group and control group. E Flowchart illustrating the identification of RRM2 transcription factors using TCGA LUAD and GSE31210 and GSE30219 datasets. F The correlation between <t>MYBL2,</t> CENPA, FOXM1, E2F1, ZNF367, and HMGA1 with RRM2 in RNA-seq data. G, H The correlation between MYBL2 and RRM2 in TCGA LUAD ( G ) and our RNA-seq ( H ). I The schematic diagram for two MYBL2 binding motifs on RRM2 promoter (FL) and related truncated (ST) and site-mutated promoter (S-mut) constructs. J Relative luciferase reporter activity of RRM2 promoter (−2000 ~ + 60) while co-transfected with MYBL2 expression plasmid for 48 h in H2122 and H23 cells. K Relative luciferase reporter activity of the truncated and site-mutated RRM2 promoters while co-transfected with MYBL2 expression plasmid for 48 h in H2122 cells. L The expression of MYBL2 and RRM2 proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h. M The expression of phosphorylation and total levels of ERK and AKT proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h.
Mybl2, supplied by Proteintech, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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96
Santa Cruz Biotechnology anti caspase 9
A GSEA analysis comparing sotorasib, adavosertib, and combination groups to the control group, as well as comparing the combination group to sotorasib and adavosertib groups. B NES values of E2F targets and G2M checkpoint pathways in GSEA analysis, with pairwise comparisons among the four treatment groups. C Venn diagram of the top 20 genes in E2F targets pathway comparing the combination group to sotorasib group, adavosertib group and control group. D Venn diagram of the top 20 genes in G2M checkpoint pathway comparing the combination group to sotorasib group, adavosertib group and control group. E Flowchart illustrating the identification of RRM2 transcription factors using TCGA LUAD and GSE31210 and GSE30219 datasets. F The correlation between <t>MYBL2,</t> CENPA, FOXM1, E2F1, ZNF367, and HMGA1 with RRM2 in RNA-seq data. G, H The correlation between MYBL2 and RRM2 in TCGA LUAD ( G ) and our RNA-seq ( H ). I The schematic diagram for two MYBL2 binding motifs on RRM2 promoter (FL) and related truncated (ST) and site-mutated promoter (S-mut) constructs. J Relative luciferase reporter activity of RRM2 promoter (−2000 ~ + 60) while co-transfected with MYBL2 expression plasmid for 48 h in H2122 and H23 cells. K Relative luciferase reporter activity of the truncated and site-mutated RRM2 promoters while co-transfected with MYBL2 expression plasmid for 48 h in H2122 cells. L The expression of MYBL2 and RRM2 proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h. M The expression of phosphorylation and total levels of ERK and AKT proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h.
Anti Caspase 9, supplied by Santa Cruz Biotechnology, used in various techniques. Bioz Stars score: 96/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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Proteintech tumor cell death
A GSEA analysis comparing sotorasib, adavosertib, and combination groups to the control group, as well as comparing the combination group to sotorasib and adavosertib groups. B NES values of E2F targets and G2M checkpoint pathways in GSEA analysis, with pairwise comparisons among the four treatment groups. C Venn diagram of the top 20 genes in E2F targets pathway comparing the combination group to sotorasib group, adavosertib group and control group. D Venn diagram of the top 20 genes in G2M checkpoint pathway comparing the combination group to sotorasib group, adavosertib group and control group. E Flowchart illustrating the identification of RRM2 transcription factors using TCGA LUAD and GSE31210 and GSE30219 datasets. F The correlation between <t>MYBL2,</t> CENPA, FOXM1, E2F1, ZNF367, and HMGA1 with RRM2 in RNA-seq data. G, H The correlation between MYBL2 and RRM2 in TCGA LUAD ( G ) and our RNA-seq ( H ). I The schematic diagram for two MYBL2 binding motifs on RRM2 promoter (FL) and related truncated (ST) and site-mutated promoter (S-mut) constructs. J Relative luciferase reporter activity of RRM2 promoter (−2000 ~ + 60) while co-transfected with MYBL2 expression plasmid for 48 h in H2122 and H23 cells. K Relative luciferase reporter activity of the truncated and site-mutated RRM2 promoters while co-transfected with MYBL2 expression plasmid for 48 h in H2122 cells. L The expression of MYBL2 and RRM2 proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h. M The expression of phosphorylation and total levels of ERK and AKT proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h.
Tumor Cell Death, supplied by Proteintech, used in various techniques. Bioz Stars score: 96/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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Proteintech anti ercc1 monoclonal antibody
Figure 1. Biomarker expression by was evaluated by immunohistochemistry. These photomicrographs reveal (a) low excision cross-complementing gene-1 <t>(ERCC1)</t> expression, (b) high ERCC1 expression, (c) low ribonucleotide reductase subunit M1 (RRM1) expression, (d) high RRM1 expression, (e) low ribonucleotide reductase subunit M2 (RRM2) expression, (f) high RRM2 expression, (g) low human equilibrative nucleoside transporter 1 (hENT1) expression, and (h) high hENT1 expression (original magnification, 400 in a-h).
Anti Ercc1 Monoclonal Antibody, supplied by Proteintech, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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93
Proteintech anti rrm1 polyclonal antibody
Figure 1. Biomarker expression by was evaluated by immunohistochemistry. These photomicrographs reveal (a) low excision cross-complementing gene-1 (ERCC1) expression, (b) high ERCC1 expression, (c) low ribonucleotide reductase subunit M1 <t>(RRM1)</t> expression, (d) high RRM1 expression, (e) low ribonucleotide reductase subunit M2 (RRM2) expression, (f) high RRM2 expression, (g) low human equilibrative nucleoside transporter 1 (hENT1) expression, and (h) high hENT1 expression (original magnification, 400 in a-h).
Anti Rrm1 Polyclonal Antibody, supplied by Proteintech, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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Solexa biotinylation pre existing rna newly synthesized rna solexa sequencing
Figure 1. Biomarker expression by was evaluated by immunohistochemistry. These photomicrographs reveal (a) low excision cross-complementing gene-1 (ERCC1) expression, (b) high ERCC1 expression, (c) low ribonucleotide reductase subunit M1 <t>(RRM1)</t> expression, (d) high RRM1 expression, (e) low ribonucleotide reductase subunit M2 (RRM2) expression, (f) high RRM2 expression, (g) low human equilibrative nucleoside transporter 1 (hENT1) expression, and (h) high hENT1 expression (original magnification, 400 in a-h).
Biotinylation Pre Existing Rna Newly Synthesized Rna Solexa Sequencing, supplied by Solexa, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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Image Search Results


A GSEA analysis comparing sotorasib, adavosertib, and combination groups to the control group, as well as comparing the combination group to sotorasib and adavosertib groups. B NES values of E2F targets and G2M checkpoint pathways in GSEA analysis, with pairwise comparisons among the four treatment groups. C Venn diagram of the top 20 genes in E2F targets pathway comparing the combination group to sotorasib group, adavosertib group and control group. D Venn diagram of the top 20 genes in G2M checkpoint pathway comparing the combination group to sotorasib group, adavosertib group and control group. E Flowchart illustrating the identification of RRM2 transcription factors using TCGA LUAD and GSE31210 and GSE30219 datasets. F The correlation between MYBL2, CENPA, FOXM1, E2F1, ZNF367, and HMGA1 with RRM2 in RNA-seq data. G, H The correlation between MYBL2 and RRM2 in TCGA LUAD ( G ) and our RNA-seq ( H ). I The schematic diagram for two MYBL2 binding motifs on RRM2 promoter (FL) and related truncated (ST) and site-mutated promoter (S-mut) constructs. J Relative luciferase reporter activity of RRM2 promoter (−2000 ~ + 60) while co-transfected with MYBL2 expression plasmid for 48 h in H2122 and H23 cells. K Relative luciferase reporter activity of the truncated and site-mutated RRM2 promoters while co-transfected with MYBL2 expression plasmid for 48 h in H2122 cells. L The expression of MYBL2 and RRM2 proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h. M The expression of phosphorylation and total levels of ERK and AKT proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h.

Journal: Cell Death & Disease

Article Title: WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRAS G12C -mutant lung cancer

doi: 10.1038/s41419-025-07992-4

Figure Lengend Snippet: A GSEA analysis comparing sotorasib, adavosertib, and combination groups to the control group, as well as comparing the combination group to sotorasib and adavosertib groups. B NES values of E2F targets and G2M checkpoint pathways in GSEA analysis, with pairwise comparisons among the four treatment groups. C Venn diagram of the top 20 genes in E2F targets pathway comparing the combination group to sotorasib group, adavosertib group and control group. D Venn diagram of the top 20 genes in G2M checkpoint pathway comparing the combination group to sotorasib group, adavosertib group and control group. E Flowchart illustrating the identification of RRM2 transcription factors using TCGA LUAD and GSE31210 and GSE30219 datasets. F The correlation between MYBL2, CENPA, FOXM1, E2F1, ZNF367, and HMGA1 with RRM2 in RNA-seq data. G, H The correlation between MYBL2 and RRM2 in TCGA LUAD ( G ) and our RNA-seq ( H ). I The schematic diagram for two MYBL2 binding motifs on RRM2 promoter (FL) and related truncated (ST) and site-mutated promoter (S-mut) constructs. J Relative luciferase reporter activity of RRM2 promoter (−2000 ~ + 60) while co-transfected with MYBL2 expression plasmid for 48 h in H2122 and H23 cells. K Relative luciferase reporter activity of the truncated and site-mutated RRM2 promoters while co-transfected with MYBL2 expression plasmid for 48 h in H2122 cells. L The expression of MYBL2 and RRM2 proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h. M The expression of phosphorylation and total levels of ERK and AKT proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h.

Article Snippet: For IHC staining, Ki67, MYBL2, RRM2, and γH2AX protein levels in the tumor samples harvested from mice were assessed by IHC using anti-Ki67 (1:1600 dilution, ABclonal), anti-MYBL2 (1:1000 dilution, Proteintech), anti-RRM2 (1:1200 dilution, ABclonal), and anti-γH2AX (1:800 dilution, ABclonal).

Techniques: Control, RNA Sequencing, Binding Assay, Construct, Luciferase, Activity Assay, Transfection, Expressing, Plasmid Preparation, Phospho-proteomics

A, B Comparison of MYBL2 ( A ) and RRM2 ( B ) expression in normal lung tissue and early-stage lung adenocarcinoma tumors or in tumor tissues from non-relapsed and relapsed lung cancer patients in the GSE31210 dataset. C, D Comparison of MYBL2 ( C ) and RRM2 ( D ) expression at different stages in the GSE31210 dataset. E, F Relapse free survival probability of two groups classified by MYBL2 ( E ) or RRM2 ( F ) median expression levels in the GSE31210 dataset. G The expression of MYBL2 and RRM2 proteins in normal lung epithelial cells (NOR) and NSCLC cells (NSCLC). H Representative IHC images of MYBL2 and RRM2 expression in LUAD tissue microarray. I RRM2 expression levels in high and low expression groups based on the median value of MYBL2. J The correlation between MYBL2 and RRM2 IHC H score in LUAD tissue microarray. K Comparison of MYBL2 and RRM2 expression at different stages in the LUAD tissue microarray. L Percent survival probability of two groups classified by MYBL2 or RRM2 median expression levels in the LUAD tissue microarray. M Percent survival probability of four patient groups classified by the median expression levels of MYBL2 or RRM2 in the LUAD tissue microarray.

Journal: Cell Death & Disease

Article Title: WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRAS G12C -mutant lung cancer

doi: 10.1038/s41419-025-07992-4

Figure Lengend Snippet: A, B Comparison of MYBL2 ( A ) and RRM2 ( B ) expression in normal lung tissue and early-stage lung adenocarcinoma tumors or in tumor tissues from non-relapsed and relapsed lung cancer patients in the GSE31210 dataset. C, D Comparison of MYBL2 ( C ) and RRM2 ( D ) expression at different stages in the GSE31210 dataset. E, F Relapse free survival probability of two groups classified by MYBL2 ( E ) or RRM2 ( F ) median expression levels in the GSE31210 dataset. G The expression of MYBL2 and RRM2 proteins in normal lung epithelial cells (NOR) and NSCLC cells (NSCLC). H Representative IHC images of MYBL2 and RRM2 expression in LUAD tissue microarray. I RRM2 expression levels in high and low expression groups based on the median value of MYBL2. J The correlation between MYBL2 and RRM2 IHC H score in LUAD tissue microarray. K Comparison of MYBL2 and RRM2 expression at different stages in the LUAD tissue microarray. L Percent survival probability of two groups classified by MYBL2 or RRM2 median expression levels in the LUAD tissue microarray. M Percent survival probability of four patient groups classified by the median expression levels of MYBL2 or RRM2 in the LUAD tissue microarray.

Article Snippet: For IHC staining, Ki67, MYBL2, RRM2, and γH2AX protein levels in the tumor samples harvested from mice were assessed by IHC using anti-Ki67 (1:1600 dilution, ABclonal), anti-MYBL2 (1:1000 dilution, Proteintech), anti-RRM2 (1:1200 dilution, ABclonal), and anti-γH2AX (1:800 dilution, ABclonal).

Techniques: Comparison, Expressing, Microarray

A The expression of MYBL2 and RRM2 proteins in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 72 h. B Representative images of colony formation in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 10–14 days. C Representative images and proportion of EdU incorporation assay in H2122 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. n = 3 per group. D Representative images and proportion of γH2AX positive cells in H2122 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. n = 3 per group. E Representative images of cell apoptosis assay in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. F Cell apoptosis proportion in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. n = 3 per group. G The expression of MYBL2 and RRM2 proteins in H2122 and H23 cells under empty vector (EV), MYBL2 or RRM2 plasmids treatment for 48 h. H Representative images of colony formation H2122 and H23 cells under EV, MYBL2 or RRM2 plasmids treatment for 10–14 days. I The cell viability of H2122 cells overexpressing EV, MYBL2, and RRM2 under control, sotorasib, adavosertib or combination treatment for 72 h. n = 3 per group. J The cell growth of H2122 and H23 cells overexpressing EV, MYBL2, and RRM2 under combination of sotorasib and adavosertib treatment for 72 h. K Representative images of colony formation in H2122 and H23 cells overexpressing EV, MYBL2, and RRM2 under combination of sotorasib and adavosertib treatment for 10-14 days. L, M Representative images ( L ) and proportion ( M ) of EdU positive cells in H2122 cells overexpressing EV, MYBL2, and RRM2 under control, sotorasib, adavosertib or combination treatment for 48 h. n = 3 per group. Data are mean ± SD of three independent replicates.

Journal: Cell Death & Disease

Article Title: WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRAS G12C -mutant lung cancer

doi: 10.1038/s41419-025-07992-4

Figure Lengend Snippet: A The expression of MYBL2 and RRM2 proteins in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 72 h. B Representative images of colony formation in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 10–14 days. C Representative images and proportion of EdU incorporation assay in H2122 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. n = 3 per group. D Representative images and proportion of γH2AX positive cells in H2122 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. n = 3 per group. E Representative images of cell apoptosis assay in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. F Cell apoptosis proportion in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. n = 3 per group. G The expression of MYBL2 and RRM2 proteins in H2122 and H23 cells under empty vector (EV), MYBL2 or RRM2 plasmids treatment for 48 h. H Representative images of colony formation H2122 and H23 cells under EV, MYBL2 or RRM2 plasmids treatment for 10–14 days. I The cell viability of H2122 cells overexpressing EV, MYBL2, and RRM2 under control, sotorasib, adavosertib or combination treatment for 72 h. n = 3 per group. J The cell growth of H2122 and H23 cells overexpressing EV, MYBL2, and RRM2 under combination of sotorasib and adavosertib treatment for 72 h. K Representative images of colony formation in H2122 and H23 cells overexpressing EV, MYBL2, and RRM2 under combination of sotorasib and adavosertib treatment for 10-14 days. L, M Representative images ( L ) and proportion ( M ) of EdU positive cells in H2122 cells overexpressing EV, MYBL2, and RRM2 under control, sotorasib, adavosertib or combination treatment for 48 h. n = 3 per group. Data are mean ± SD of three independent replicates.

Article Snippet: For IHC staining, Ki67, MYBL2, RRM2, and γH2AX protein levels in the tumor samples harvested from mice were assessed by IHC using anti-Ki67 (1:1600 dilution, ABclonal), anti-MYBL2 (1:1000 dilution, Proteintech), anti-RRM2 (1:1200 dilution, ABclonal), and anti-γH2AX (1:800 dilution, ABclonal).

Techniques: Expressing, Apoptosis Assay, Plasmid Preparation, Control

A Diagram illustrating the function of RRM2. B The cell viability of H2122 and H23 cells under control, sotorasib, adavosertib or combination treatment for 72 h with and without 10 μM dNTPs or dNs. n = 3 per group. C The cell growth of H2122 and H23 cells under combination of sotorasib and adavosertib treatment for 72 h with and without 10 μM dNTPs or dNs. D Representative images of colony formation in H2122 and H23 cells under combination of sotorasib and adavosertib treatment for 10–14 days with and without dNTPs or dNs. E, F Representative images ( E ) and proportion ( F ) of EdU positive in H2122 cells under control, sotorasib, adavosertib or combination treatment for 48 h with and without 10 μM dNTPs. n = 3 per group. G, H Representative images ( G ) and apoptosis proportion ( H ) of cell apoptosis assay in H2122 cells under control, sotorasib, adavosertib or combination treatment for 48 h with and without 10 μM dNTPs or dNs. n = 3 per group. I, J Representative images of cell cycle distribution and γH2AX positive cells in H2122 ( I ) and H23 ( J ) cells under combination treatment for 48 h with and without 10 μM dNTPs performed using flow cytometry. The cell cycle was divided into the 2 N, 4 N, S1, S2, S3, no replication S, and subG1 phases by PI and EdU. K Proportion of no replication S phase in H2122 and H23 cells under combination treatment for 48 h with and without dNTPs. n = 3 per group. L Proportion of γH2AX positive cells in H2122 and H23 cells under combination treatment for 48 h with and without dNTPs. n = 3 per group. Data are mean ± SD of three independent replicates.

Journal: Cell Death & Disease

Article Title: WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRAS G12C -mutant lung cancer

doi: 10.1038/s41419-025-07992-4

Figure Lengend Snippet: A Diagram illustrating the function of RRM2. B The cell viability of H2122 and H23 cells under control, sotorasib, adavosertib or combination treatment for 72 h with and without 10 μM dNTPs or dNs. n = 3 per group. C The cell growth of H2122 and H23 cells under combination of sotorasib and adavosertib treatment for 72 h with and without 10 μM dNTPs or dNs. D Representative images of colony formation in H2122 and H23 cells under combination of sotorasib and adavosertib treatment for 10–14 days with and without dNTPs or dNs. E, F Representative images ( E ) and proportion ( F ) of EdU positive in H2122 cells under control, sotorasib, adavosertib or combination treatment for 48 h with and without 10 μM dNTPs. n = 3 per group. G, H Representative images ( G ) and apoptosis proportion ( H ) of cell apoptosis assay in H2122 cells under control, sotorasib, adavosertib or combination treatment for 48 h with and without 10 μM dNTPs or dNs. n = 3 per group. I, J Representative images of cell cycle distribution and γH2AX positive cells in H2122 ( I ) and H23 ( J ) cells under combination treatment for 48 h with and without 10 μM dNTPs performed using flow cytometry. The cell cycle was divided into the 2 N, 4 N, S1, S2, S3, no replication S, and subG1 phases by PI and EdU. K Proportion of no replication S phase in H2122 and H23 cells under combination treatment for 48 h with and without dNTPs. n = 3 per group. L Proportion of γH2AX positive cells in H2122 and H23 cells under combination treatment for 48 h with and without dNTPs. n = 3 per group. Data are mean ± SD of three independent replicates.

Article Snippet: For IHC staining, Ki67, MYBL2, RRM2, and γH2AX protein levels in the tumor samples harvested from mice were assessed by IHC using anti-Ki67 (1:1600 dilution, ABclonal), anti-MYBL2 (1:1000 dilution, Proteintech), anti-RRM2 (1:1200 dilution, ABclonal), and anti-γH2AX (1:800 dilution, ABclonal).

Techniques: Control, Apoptosis Assay, Flow Cytometry

A H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days shown in tumor growth. n = 5 mice, with 10 tumors per group. B Percent survival in H2122 xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. Tumor volume exceeding 600 mm 3 is considered lethal. n = 10 tumors per group. C Waterfall plot analyses of changes in tumor volume at the end of treatment. n = 10 tumors per group. D Photograph of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. E Tumor mass of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. F Body weight of mice bearing H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 5 mice per group. G H&E staining, IHC staining, and TUNEL staining of xenografts tumors. Scale bar, 100 μm in the full image and 25 μm in the magnified image of the top right corner. For TUNEL staining, The blue fluorescence (DAPI) in tumor represented for tumor cells and red fluorescence (TUNEL, TMR red) represented for apoptosis tumor cells. Scale bar, 50 μm. H The staining expression of Ki67, MYBL2, RRM2, pH2AX and apoptosis index in xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. n = 9 per group. Expression is calculated using three slices per group, with three randomly selected regions per slice. I The correlation between MYBL2 and RRM2 IHC H score in xenografts tumors. n = 12. J Abstract. In KRAS-G12C mutant NSCLC, the combination of G12Ci and WEE1i synergistically suppresses the MYBL2-RRM2 axis. This suppression leads to a reduction in dNTPs, triggers DNA replication stress, and results in the accumulation of DNA damage, ultimately culminating in apoptosis. Data are mean ± SD of independent replicates.

Journal: Cell Death & Disease

Article Title: WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRAS G12C -mutant lung cancer

doi: 10.1038/s41419-025-07992-4

Figure Lengend Snippet: A H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days shown in tumor growth. n = 5 mice, with 10 tumors per group. B Percent survival in H2122 xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. Tumor volume exceeding 600 mm 3 is considered lethal. n = 10 tumors per group. C Waterfall plot analyses of changes in tumor volume at the end of treatment. n = 10 tumors per group. D Photograph of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. E Tumor mass of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. F Body weight of mice bearing H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 5 mice per group. G H&E staining, IHC staining, and TUNEL staining of xenografts tumors. Scale bar, 100 μm in the full image and 25 μm in the magnified image of the top right corner. For TUNEL staining, The blue fluorescence (DAPI) in tumor represented for tumor cells and red fluorescence (TUNEL, TMR red) represented for apoptosis tumor cells. Scale bar, 50 μm. H The staining expression of Ki67, MYBL2, RRM2, pH2AX and apoptosis index in xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. n = 9 per group. Expression is calculated using three slices per group, with three randomly selected regions per slice. I The correlation between MYBL2 and RRM2 IHC H score in xenografts tumors. n = 12. J Abstract. In KRAS-G12C mutant NSCLC, the combination of G12Ci and WEE1i synergistically suppresses the MYBL2-RRM2 axis. This suppression leads to a reduction in dNTPs, triggers DNA replication stress, and results in the accumulation of DNA damage, ultimately culminating in apoptosis. Data are mean ± SD of independent replicates.

Article Snippet: For IHC staining, Ki67, MYBL2, RRM2, and γH2AX protein levels in the tumor samples harvested from mice were assessed by IHC using anti-Ki67 (1:1600 dilution, ABclonal), anti-MYBL2 (1:1000 dilution, Proteintech), anti-RRM2 (1:1200 dilution, ABclonal), and anti-γH2AX (1:800 dilution, ABclonal).

Techniques: Staining, Immunohistochemistry, TUNEL Assay, Fluorescence, Expressing, Mutagenesis

A H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days shown in tumor growth. n = 5 mice, with 10 tumors per group. B Percent survival in H2122 xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. Tumor volume exceeding 600 mm 3 is considered lethal. n = 10 tumors per group. C Waterfall plot analyses of changes in tumor volume at the end of treatment. n = 10 tumors per group. D Photograph of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. E Tumor mass of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. F Body weight of mice bearing H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 5 mice per group. G H&E staining, IHC staining, and TUNEL staining of xenografts tumors. Scale bar, 100 μm in the full image and 25 μm in the magnified image of the top right corner. For TUNEL staining, The blue fluorescence (DAPI) in tumor represented for tumor cells and red fluorescence (TUNEL, TMR red) represented for apoptosis tumor cells. Scale bar, 50 μm. H The staining expression of Ki67, MYBL2, RRM2, pH2AX and apoptosis index in xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. n = 9 per group. Expression is calculated using three slices per group, with three randomly selected regions per slice. I The correlation between MYBL2 and RRM2 IHC H score in xenografts tumors. n = 12. J Abstract. In KRAS-G12C mutant NSCLC, the combination of G12Ci and WEE1i synergistically suppresses the MYBL2-RRM2 axis. This suppression leads to a reduction in dNTPs, triggers DNA replication stress, and results in the accumulation of DNA damage, ultimately culminating in apoptosis. Data are mean ± SD of independent replicates.

Journal: Cell Death & Disease

Article Title: WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRAS G12C -mutant lung cancer

doi: 10.1038/s41419-025-07992-4

Figure Lengend Snippet: A H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days shown in tumor growth. n = 5 mice, with 10 tumors per group. B Percent survival in H2122 xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. Tumor volume exceeding 600 mm 3 is considered lethal. n = 10 tumors per group. C Waterfall plot analyses of changes in tumor volume at the end of treatment. n = 10 tumors per group. D Photograph of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. E Tumor mass of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. F Body weight of mice bearing H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 5 mice per group. G H&E staining, IHC staining, and TUNEL staining of xenografts tumors. Scale bar, 100 μm in the full image and 25 μm in the magnified image of the top right corner. For TUNEL staining, The blue fluorescence (DAPI) in tumor represented for tumor cells and red fluorescence (TUNEL, TMR red) represented for apoptosis tumor cells. Scale bar, 50 μm. H The staining expression of Ki67, MYBL2, RRM2, pH2AX and apoptosis index in xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. n = 9 per group. Expression is calculated using three slices per group, with three randomly selected regions per slice. I The correlation between MYBL2 and RRM2 IHC H score in xenografts tumors. n = 12. J Abstract. In KRAS-G12C mutant NSCLC, the combination of G12Ci and WEE1i synergistically suppresses the MYBL2-RRM2 axis. This suppression leads to a reduction in dNTPs, triggers DNA replication stress, and results in the accumulation of DNA damage, ultimately culminating in apoptosis. Data are mean ± SD of independent replicates.

Article Snippet: For IHC staining, Ki67, MYBL2, RRM2, and γH2AX protein levels in the tumor samples harvested from mice were assessed by IHC using anti-Ki67 (1:1600 dilution, ABclonal), anti-MYBL2 (1:1000 dilution, Proteintech), anti-RRM2 (1:1200 dilution, ABclonal), and anti-γH2AX (1:800 dilution, ABclonal).

Techniques: Staining, Immunohistochemistry, TUNEL Assay, Fluorescence, Expressing, Mutagenesis

A GSEA analysis comparing sotorasib, adavosertib, and combination groups to the control group, as well as comparing the combination group to sotorasib and adavosertib groups. B NES values of E2F targets and G2M checkpoint pathways in GSEA analysis, with pairwise comparisons among the four treatment groups. C Venn diagram of the top 20 genes in E2F targets pathway comparing the combination group to sotorasib group, adavosertib group and control group. D Venn diagram of the top 20 genes in G2M checkpoint pathway comparing the combination group to sotorasib group, adavosertib group and control group. E Flowchart illustrating the identification of RRM2 transcription factors using TCGA LUAD and GSE31210 and GSE30219 datasets. F The correlation between MYBL2, CENPA, FOXM1, E2F1, ZNF367, and HMGA1 with RRM2 in RNA-seq data. G, H The correlation between MYBL2 and RRM2 in TCGA LUAD ( G ) and our RNA-seq ( H ). I The schematic diagram for two MYBL2 binding motifs on RRM2 promoter (FL) and related truncated (ST) and site-mutated promoter (S-mut) constructs. J Relative luciferase reporter activity of RRM2 promoter (−2000 ~ + 60) while co-transfected with MYBL2 expression plasmid for 48 h in H2122 and H23 cells. K Relative luciferase reporter activity of the truncated and site-mutated RRM2 promoters while co-transfected with MYBL2 expression plasmid for 48 h in H2122 cells. L The expression of MYBL2 and RRM2 proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h. M The expression of phosphorylation and total levels of ERK and AKT proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h.

Journal: Cell Death & Disease

Article Title: WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRAS G12C -mutant lung cancer

doi: 10.1038/s41419-025-07992-4

Figure Lengend Snippet: A GSEA analysis comparing sotorasib, adavosertib, and combination groups to the control group, as well as comparing the combination group to sotorasib and adavosertib groups. B NES values of E2F targets and G2M checkpoint pathways in GSEA analysis, with pairwise comparisons among the four treatment groups. C Venn diagram of the top 20 genes in E2F targets pathway comparing the combination group to sotorasib group, adavosertib group and control group. D Venn diagram of the top 20 genes in G2M checkpoint pathway comparing the combination group to sotorasib group, adavosertib group and control group. E Flowchart illustrating the identification of RRM2 transcription factors using TCGA LUAD and GSE31210 and GSE30219 datasets. F The correlation between MYBL2, CENPA, FOXM1, E2F1, ZNF367, and HMGA1 with RRM2 in RNA-seq data. G, H The correlation between MYBL2 and RRM2 in TCGA LUAD ( G ) and our RNA-seq ( H ). I The schematic diagram for two MYBL2 binding motifs on RRM2 promoter (FL) and related truncated (ST) and site-mutated promoter (S-mut) constructs. J Relative luciferase reporter activity of RRM2 promoter (−2000 ~ + 60) while co-transfected with MYBL2 expression plasmid for 48 h in H2122 and H23 cells. K Relative luciferase reporter activity of the truncated and site-mutated RRM2 promoters while co-transfected with MYBL2 expression plasmid for 48 h in H2122 cells. L The expression of MYBL2 and RRM2 proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h. M The expression of phosphorylation and total levels of ERK and AKT proteins in H2122, H23 and H358 cells under control, sotorasib, adavosertib or combination treatment for 24 h.

Article Snippet: For IHC staining, Ki67, MYBL2, RRM2, and γH2AX protein levels in the tumor samples harvested from mice were assessed by IHC using anti-Ki67 (1:1600 dilution, ABclonal), anti-MYBL2 (1:1000 dilution, Proteintech), anti-RRM2 (1:1200 dilution, ABclonal), and anti-γH2AX (1:800 dilution, ABclonal).

Techniques: Control, RNA Sequencing, Binding Assay, Construct, Luciferase, Activity Assay, Transfection, Expressing, Plasmid Preparation, Phospho-proteomics

A, B Comparison of MYBL2 ( A ) and RRM2 ( B ) expression in normal lung tissue and early-stage lung adenocarcinoma tumors or in tumor tissues from non-relapsed and relapsed lung cancer patients in the GSE31210 dataset. C, D Comparison of MYBL2 ( C ) and RRM2 ( D ) expression at different stages in the GSE31210 dataset. E, F Relapse free survival probability of two groups classified by MYBL2 ( E ) or RRM2 ( F ) median expression levels in the GSE31210 dataset. G The expression of MYBL2 and RRM2 proteins in normal lung epithelial cells (NOR) and NSCLC cells (NSCLC). H Representative IHC images of MYBL2 and RRM2 expression in LUAD tissue microarray. I RRM2 expression levels in high and low expression groups based on the median value of MYBL2. J The correlation between MYBL2 and RRM2 IHC H score in LUAD tissue microarray. K Comparison of MYBL2 and RRM2 expression at different stages in the LUAD tissue microarray. L Percent survival probability of two groups classified by MYBL2 or RRM2 median expression levels in the LUAD tissue microarray. M Percent survival probability of four patient groups classified by the median expression levels of MYBL2 or RRM2 in the LUAD tissue microarray.

Journal: Cell Death & Disease

Article Title: WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRAS G12C -mutant lung cancer

doi: 10.1038/s41419-025-07992-4

Figure Lengend Snippet: A, B Comparison of MYBL2 ( A ) and RRM2 ( B ) expression in normal lung tissue and early-stage lung adenocarcinoma tumors or in tumor tissues from non-relapsed and relapsed lung cancer patients in the GSE31210 dataset. C, D Comparison of MYBL2 ( C ) and RRM2 ( D ) expression at different stages in the GSE31210 dataset. E, F Relapse free survival probability of two groups classified by MYBL2 ( E ) or RRM2 ( F ) median expression levels in the GSE31210 dataset. G The expression of MYBL2 and RRM2 proteins in normal lung epithelial cells (NOR) and NSCLC cells (NSCLC). H Representative IHC images of MYBL2 and RRM2 expression in LUAD tissue microarray. I RRM2 expression levels in high and low expression groups based on the median value of MYBL2. J The correlation between MYBL2 and RRM2 IHC H score in LUAD tissue microarray. K Comparison of MYBL2 and RRM2 expression at different stages in the LUAD tissue microarray. L Percent survival probability of two groups classified by MYBL2 or RRM2 median expression levels in the LUAD tissue microarray. M Percent survival probability of four patient groups classified by the median expression levels of MYBL2 or RRM2 in the LUAD tissue microarray.

Article Snippet: For IHC staining, Ki67, MYBL2, RRM2, and γH2AX protein levels in the tumor samples harvested from mice were assessed by IHC using anti-Ki67 (1:1600 dilution, ABclonal), anti-MYBL2 (1:1000 dilution, Proteintech), anti-RRM2 (1:1200 dilution, ABclonal), and anti-γH2AX (1:800 dilution, ABclonal).

Techniques: Comparison, Expressing, Microarray

A The expression of MYBL2 and RRM2 proteins in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 72 h. B Representative images of colony formation in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 10–14 days. C Representative images and proportion of EdU incorporation assay in H2122 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. n = 3 per group. D Representative images and proportion of γH2AX positive cells in H2122 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. n = 3 per group. E Representative images of cell apoptosis assay in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. F Cell apoptosis proportion in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. n = 3 per group. G The expression of MYBL2 and RRM2 proteins in H2122 and H23 cells under empty vector (EV), MYBL2 or RRM2 plasmids treatment for 48 h. H Representative images of colony formation H2122 and H23 cells under EV, MYBL2 or RRM2 plasmids treatment for 10–14 days. I The cell viability of H2122 cells overexpressing EV, MYBL2, and RRM2 under control, sotorasib, adavosertib or combination treatment for 72 h. n = 3 per group. J The cell growth of H2122 and H23 cells overexpressing EV, MYBL2, and RRM2 under combination of sotorasib and adavosertib treatment for 72 h. K Representative images of colony formation in H2122 and H23 cells overexpressing EV, MYBL2, and RRM2 under combination of sotorasib and adavosertib treatment for 10-14 days. L, M Representative images ( L ) and proportion ( M ) of EdU positive cells in H2122 cells overexpressing EV, MYBL2, and RRM2 under control, sotorasib, adavosertib or combination treatment for 48 h. n = 3 per group. Data are mean ± SD of three independent replicates.

Journal: Cell Death & Disease

Article Title: WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRAS G12C -mutant lung cancer

doi: 10.1038/s41419-025-07992-4

Figure Lengend Snippet: A The expression of MYBL2 and RRM2 proteins in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 72 h. B Representative images of colony formation in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 10–14 days. C Representative images and proportion of EdU incorporation assay in H2122 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. n = 3 per group. D Representative images and proportion of γH2AX positive cells in H2122 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. n = 3 per group. E Representative images of cell apoptosis assay in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. F Cell apoptosis proportion in H2122 and H23 cells under mock, siMYBL2 or siRRM2 treatment for 48 h. n = 3 per group. G The expression of MYBL2 and RRM2 proteins in H2122 and H23 cells under empty vector (EV), MYBL2 or RRM2 plasmids treatment for 48 h. H Representative images of colony formation H2122 and H23 cells under EV, MYBL2 or RRM2 plasmids treatment for 10–14 days. I The cell viability of H2122 cells overexpressing EV, MYBL2, and RRM2 under control, sotorasib, adavosertib or combination treatment for 72 h. n = 3 per group. J The cell growth of H2122 and H23 cells overexpressing EV, MYBL2, and RRM2 under combination of sotorasib and adavosertib treatment for 72 h. K Representative images of colony formation in H2122 and H23 cells overexpressing EV, MYBL2, and RRM2 under combination of sotorasib and adavosertib treatment for 10-14 days. L, M Representative images ( L ) and proportion ( M ) of EdU positive cells in H2122 cells overexpressing EV, MYBL2, and RRM2 under control, sotorasib, adavosertib or combination treatment for 48 h. n = 3 per group. Data are mean ± SD of three independent replicates.

Article Snippet: For IHC staining, Ki67, MYBL2, RRM2, and γH2AX protein levels in the tumor samples harvested from mice were assessed by IHC using anti-Ki67 (1:1600 dilution, ABclonal), anti-MYBL2 (1:1000 dilution, Proteintech), anti-RRM2 (1:1200 dilution, ABclonal), and anti-γH2AX (1:800 dilution, ABclonal).

Techniques: Expressing, Apoptosis Assay, Plasmid Preparation, Control

A H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days shown in tumor growth. n = 5 mice, with 10 tumors per group. B Percent survival in H2122 xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. Tumor volume exceeding 600 mm 3 is considered lethal. n = 10 tumors per group. C Waterfall plot analyses of changes in tumor volume at the end of treatment. n = 10 tumors per group. D Photograph of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. E Tumor mass of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. F Body weight of mice bearing H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 5 mice per group. G H&E staining, IHC staining, and TUNEL staining of xenografts tumors. Scale bar, 100 μm in the full image and 25 μm in the magnified image of the top right corner. For TUNEL staining, The blue fluorescence (DAPI) in tumor represented for tumor cells and red fluorescence (TUNEL, TMR red) represented for apoptosis tumor cells. Scale bar, 50 μm. H The staining expression of Ki67, MYBL2, RRM2, pH2AX and apoptosis index in xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. n = 9 per group. Expression is calculated using three slices per group, with three randomly selected regions per slice. I The correlation between MYBL2 and RRM2 IHC H score in xenografts tumors. n = 12. J Abstract. In KRAS-G12C mutant NSCLC, the combination of G12Ci and WEE1i synergistically suppresses the MYBL2-RRM2 axis. This suppression leads to a reduction in dNTPs, triggers DNA replication stress, and results in the accumulation of DNA damage, ultimately culminating in apoptosis. Data are mean ± SD of independent replicates.

Journal: Cell Death & Disease

Article Title: WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRAS G12C -mutant lung cancer

doi: 10.1038/s41419-025-07992-4

Figure Lengend Snippet: A H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days shown in tumor growth. n = 5 mice, with 10 tumors per group. B Percent survival in H2122 xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. Tumor volume exceeding 600 mm 3 is considered lethal. n = 10 tumors per group. C Waterfall plot analyses of changes in tumor volume at the end of treatment. n = 10 tumors per group. D Photograph of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. E Tumor mass of xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 10 tumors per group. F Body weight of mice bearing H2122 xenografts tumors treated with sotorasib, adavosertib, or a combination of both for 18 days. n = 5 mice per group. G H&E staining, IHC staining, and TUNEL staining of xenografts tumors. Scale bar, 100 μm in the full image and 25 μm in the magnified image of the top right corner. For TUNEL staining, The blue fluorescence (DAPI) in tumor represented for tumor cells and red fluorescence (TUNEL, TMR red) represented for apoptosis tumor cells. Scale bar, 50 μm. H The staining expression of Ki67, MYBL2, RRM2, pH2AX and apoptosis index in xenografts tumors treated with sotorasib, adavosertib, or their combination for 18 days. n = 9 per group. Expression is calculated using three slices per group, with three randomly selected regions per slice. I The correlation between MYBL2 and RRM2 IHC H score in xenografts tumors. n = 12. J Abstract. In KRAS-G12C mutant NSCLC, the combination of G12Ci and WEE1i synergistically suppresses the MYBL2-RRM2 axis. This suppression leads to a reduction in dNTPs, triggers DNA replication stress, and results in the accumulation of DNA damage, ultimately culminating in apoptosis. Data are mean ± SD of independent replicates.

Article Snippet: For IHC staining, Ki67, MYBL2, RRM2, and γH2AX protein levels in the tumor samples harvested from mice were assessed by IHC using anti-Ki67 (1:1600 dilution, ABclonal), anti-MYBL2 (1:1000 dilution, Proteintech), anti-RRM2 (1:1200 dilution, ABclonal), and anti-γH2AX (1:800 dilution, ABclonal).

Techniques: Staining, Immunohistochemistry, TUNEL Assay, Fluorescence, Expressing, Mutagenesis

Figure 1. Biomarker expression by was evaluated by immunohistochemistry. These photomicrographs reveal (a) low excision cross-complementing gene-1 (ERCC1) expression, (b) high ERCC1 expression, (c) low ribonucleotide reductase subunit M1 (RRM1) expression, (d) high RRM1 expression, (e) low ribonucleotide reductase subunit M2 (RRM2) expression, (f) high RRM2 expression, (g) low human equilibrative nucleoside transporter 1 (hENT1) expression, and (h) high hENT1 expression (original magnification, 400 in a-h).

Journal: Cancer

Article Title: Excision repair cross-complementing gene-1, ribonucleotide reductase subunit M1, ribonucleotide reductase subunit M2, and human equilibrative nucleoside transporter-1 expression and prognostic value in biliary tract malignancy.

doi: 10.1002/cncr.27739

Figure Lengend Snippet: Figure 1. Biomarker expression by was evaluated by immunohistochemistry. These photomicrographs reveal (a) low excision cross-complementing gene-1 (ERCC1) expression, (b) high ERCC1 expression, (c) low ribonucleotide reductase subunit M1 (RRM1) expression, (d) high RRM1 expression, (e) low ribonucleotide reductase subunit M2 (RRM2) expression, (f) high RRM2 expression, (g) low human equilibrative nucleoside transporter 1 (hENT1) expression, and (h) high hENT1 expression (original magnification, 400 in a-h).

Article Snippet: Tissue was reacted with anti-ERCC1 monoclonal antibody (clone 8F1; Neomarkers, Fremont, Calif), anti-RRM1 polyclonal antibody (clone AD203; ProteinTech, Chicago, Ill), anti-RRM2 monoclonal antibody (clone 1E1; SigmaAldrich, St. Louis, Mo), and anti-hENT1 polyclonal antibody (polyclonal SLC29A1a; Sigma-Aldrich) to determine levels of tumor expression of ERCC1, RRM1, RRM2, and hENT1, respectively.

Techniques: Biomarker Discovery, Expressing, Immunohistochemistry

Figure 2. Overall survival (excluding 30-day mortality) is illustrated according to biomarker expression for (a) excision cross- complementing gene-1 (ERCC1), (b) ribonucleotide reductase subunit M1 (RRM1), (c) RRM2, and (d) human equilibrative nucleo- side transporter 1 (hENT1).

Journal: Cancer

Article Title: Excision repair cross-complementing gene-1, ribonucleotide reductase subunit M1, ribonucleotide reductase subunit M2, and human equilibrative nucleoside transporter-1 expression and prognostic value in biliary tract malignancy.

doi: 10.1002/cncr.27739

Figure Lengend Snippet: Figure 2. Overall survival (excluding 30-day mortality) is illustrated according to biomarker expression for (a) excision cross- complementing gene-1 (ERCC1), (b) ribonucleotide reductase subunit M1 (RRM1), (c) RRM2, and (d) human equilibrative nucleo- side transporter 1 (hENT1).

Article Snippet: Tissue was reacted with anti-ERCC1 monoclonal antibody (clone 8F1; Neomarkers, Fremont, Calif), anti-RRM1 polyclonal antibody (clone AD203; ProteinTech, Chicago, Ill), anti-RRM2 monoclonal antibody (clone 1E1; SigmaAldrich, St. Louis, Mo), and anti-hENT1 polyclonal antibody (polyclonal SLC29A1a; Sigma-Aldrich) to determine levels of tumor expression of ERCC1, RRM1, RRM2, and hENT1, respectively.

Techniques: Biomarker Discovery, Expressing

Figure 1. Biomarker expression by was evaluated by immunohistochemistry. These photomicrographs reveal (a) low excision cross-complementing gene-1 (ERCC1) expression, (b) high ERCC1 expression, (c) low ribonucleotide reductase subunit M1 (RRM1) expression, (d) high RRM1 expression, (e) low ribonucleotide reductase subunit M2 (RRM2) expression, (f) high RRM2 expression, (g) low human equilibrative nucleoside transporter 1 (hENT1) expression, and (h) high hENT1 expression (original magnification, 400 in a-h).

Journal: Cancer

Article Title: Excision repair cross-complementing gene-1, ribonucleotide reductase subunit M1, ribonucleotide reductase subunit M2, and human equilibrative nucleoside transporter-1 expression and prognostic value in biliary tract malignancy.

doi: 10.1002/cncr.27739

Figure Lengend Snippet: Figure 1. Biomarker expression by was evaluated by immunohistochemistry. These photomicrographs reveal (a) low excision cross-complementing gene-1 (ERCC1) expression, (b) high ERCC1 expression, (c) low ribonucleotide reductase subunit M1 (RRM1) expression, (d) high RRM1 expression, (e) low ribonucleotide reductase subunit M2 (RRM2) expression, (f) high RRM2 expression, (g) low human equilibrative nucleoside transporter 1 (hENT1) expression, and (h) high hENT1 expression (original magnification, 400 in a-h).

Article Snippet: Tissue was reacted with anti-ERCC1 monoclonal antibody (clone 8F1; Neomarkers, Fremont, Calif), anti-RRM1 polyclonal antibody (clone AD203; ProteinTech, Chicago, Ill), anti-RRM2 monoclonal antibody (clone 1E1; SigmaAldrich, St. Louis, Mo), and anti-hENT1 polyclonal antibody (polyclonal SLC29A1a; Sigma-Aldrich) to determine levels of tumor expression of ERCC1, RRM1, RRM2, and hENT1, respectively.

Techniques: Biomarker Discovery, Expressing, Immunohistochemistry

Figure 2. Overall survival (excluding 30-day mortality) is illustrated according to biomarker expression for (a) excision cross- complementing gene-1 (ERCC1), (b) ribonucleotide reductase subunit M1 (RRM1), (c) RRM2, and (d) human equilibrative nucleo- side transporter 1 (hENT1).

Journal: Cancer

Article Title: Excision repair cross-complementing gene-1, ribonucleotide reductase subunit M1, ribonucleotide reductase subunit M2, and human equilibrative nucleoside transporter-1 expression and prognostic value in biliary tract malignancy.

doi: 10.1002/cncr.27739

Figure Lengend Snippet: Figure 2. Overall survival (excluding 30-day mortality) is illustrated according to biomarker expression for (a) excision cross- complementing gene-1 (ERCC1), (b) ribonucleotide reductase subunit M1 (RRM1), (c) RRM2, and (d) human equilibrative nucleo- side transporter 1 (hENT1).

Article Snippet: Tissue was reacted with anti-ERCC1 monoclonal antibody (clone 8F1; Neomarkers, Fremont, Calif), anti-RRM1 polyclonal antibody (clone AD203; ProteinTech, Chicago, Ill), anti-RRM2 monoclonal antibody (clone 1E1; SigmaAldrich, St. Louis, Mo), and anti-hENT1 polyclonal antibody (polyclonal SLC29A1a; Sigma-Aldrich) to determine levels of tumor expression of ERCC1, RRM1, RRM2, and hENT1, respectively.

Techniques: Biomarker Discovery, Expressing