Journal: Neoplasia (New York, N.Y.)

Article Title: Metabolic regulation of histone acetylation by ACLY supports MDR1 expression in colorectal cancer and highlights a targetable vulnerability

doi: 10.1016/j.neo.2026.101314

Figure Lengend Snippet: ACLY activity regulates MDR1 expression in colorectal cancer. (A) Transcript levels of ACLY and MDR1 (ABCB1) in colorectal cancer (red) and normal colon tissues (grey) analyzed using GEPIA (TCGA/GTEx datasets). (B) Immunoblot analysis of MDR1 in SW480 and DLD1 cells treated with the ACLY inhibitor BMS-303141 (20 or 50 μM, 48 h). (C) Immunoblot analysis of ACLY and MDR1 in SW480 and DLD1 cells transduced with empty vector (pLV) or ACLY-overexpressing vector (pLV[Exp]-hACLY). (D) Immunoblot analysis of ACLY and MDR1 in control and ACLY-overexpressing cells treated with BMS-303141 (50 μM, 48 h). (E) Relative ABCB1 mRNA levels in control and ACLY-overexpressing cells, and in cells treated with BMS-303141. (F) Relative ACLY mRNA levels under the same conditions. Data are presented as mean ± SD (n = 3 unless otherwise indicated). Statistical significance was determined using unpaired two-tailed t-tests or one-way ANOVA with Tukey’s post hoc test. *P < 0.05; **P < 0.01; ***P < 0.001.

Article Snippet: Human colorectal cancer cell lines SW480 (KRASG12V) and DLD1 (KRASG13D) were obtained from the American Type Culture Collection (ATCC) and authenticated by short tandem repeat profiling.

Techniques: Activity Assay, Expressing, Western Blot, Transduction, Plasmid Preparation, Control, Two Tailed Test

Journal: Neoplasia (New York, N.Y.)

Article Title: Metabolic regulation of histone acetylation by ACLY supports MDR1 expression in colorectal cancer and highlights a targetable vulnerability

doi: 10.1016/j.neo.2026.101314

Figure Lengend Snippet: ACLY activity modulates histone acetylation and MDR1 expression. (A) Immunoblot analysis of MDR1 in SW480 and DLD1 cells treated with the histone deacetylase inhibitor vorinostat (VOR; 0.5 μM for SW480 and 3.5 μM for DLD1) or DMSO for 24 h. Representative blots and densitometric quantification relative to control are shown. (B) Immunoblot analysis of acetylated histone H3 (H3K9ac) and histone H4 (H4K16ac) in SW480 wild-type (WT) and ACLY-overexpressing (OE) cells treated with vehicle or the ACLY inhibitor BMS-303141 (50 μM, 48 h). (C) Immunoblot analysis of H3K9ac and H4K16ac in DLD1 cells under the same conditions. β-actin was used as a loading control. Data are presented as mean ± SD (n = 3). Statistical significance was determined using unpaired two-tailed t-tests. *P < 0.05; **P < 0.01; ***P < 0.001.

Article Snippet: Human colorectal cancer cell lines SW480 (KRASG12V) and DLD1 (KRASG13D) were obtained from the American Type Culture Collection (ATCC) and authenticated by short tandem repeat profiling.

Techniques: Activity Assay, Expressing, Western Blot, Histone Deacetylase Assay, Control, Two Tailed Test

Journal: Neoplasia (New York, N.Y.)

Article Title: Metabolic regulation of histone acetylation by ACLY supports MDR1 expression in colorectal cancer and highlights a targetable vulnerability

doi: 10.1016/j.neo.2026.101314

Figure Lengend Snippet: ACLY expression is associated with resistance-related transcriptional programs in colorectal cancer. (A) Correlation analysis between ACLY expression and a gene set associated with lipid metabolism (ACLY, ACSS2, ACSS1, FASN, SREBP1) and drug transport pathways (ABCB1, ABCC2, ABCG5, EpCAM, CD24) in colorectal cancer samples using GEPIA2 (TCGA dataset). (B) Schematic representation of a proposed model linking ACLY-dependent acetyl-CoA production to histone acetylation and transcriptional regulation in CRC cells. (C) Relative mRNA expression of EpCAM, ABCC2, and CD24 in SW480 and DLD1 cells overexpressing ACLY compared with empty vector controls. (D) Relative mRNA expression of EpCAM, ABCC2, and CD24 in SW480 and DLD1 cells treated with the ACLY inhibitor BMS-303141 (50 μM) compared with vehicle-treated controls. Gene expression levels were determined by qPCR and normalized to ACTB. Data are presented as mean ± SEM (n = 3). Statistical significance was determined using unpaired two-tailed t-tests. *P < 0.05; **P < 0.01; ***P < 0.001.

Article Snippet: Human colorectal cancer cell lines SW480 (KRASG12V) and DLD1 (KRASG13D) were obtained from the American Type Culture Collection (ATCC) and authenticated by short tandem repeat profiling.

Techniques: Expressing, Drug Transport Assay, Plasmid Preparation, Gene Expression, Two Tailed Test

Journal: Neoplasia (New York, N.Y.)

Article Title: Metabolic regulation of histone acetylation by ACLY supports MDR1 expression in colorectal cancer and highlights a targetable vulnerability

doi: 10.1016/j.neo.2026.101314

Figure Lengend Snippet: Vitamin C induces coordinated changes in metabolic and chromatin-associated pathways in colorectal cancer cells. (A) Gene Ontology (GO) enrichment analysis of proteins differentially expressed following vitamin C treatment (5 mM, 4 h). (B) Volcano plot showing significantly upregulated and downregulated proteins (log₂ fold change > 1, p < 0.05). (C) KEGG pathway enrichment analysis highlighting pathways related to chromatin organization, DNA replication, nucleotide metabolism, and cell cycle regulation. (D) GO Cellular Component analysis showing enrichment of chromatin-associated complexes, including transcription regulator complexes, histone acetyltransferase-containing complexes, and Polycomb group (PcG) assemblies. (E) Heatmap representation of differentially expressed chromatin-associated proteins in control and vitamin C-treated cells. Proteomic analysis was performed in SW480 and DLD1 cells using label-free LC–MS/MS (diaPASEF). Data represent combined analysis of both cell lines.

Article Snippet: Human colorectal cancer cell lines SW480 (KRASG12V) and DLD1 (KRASG13D) were obtained from the American Type Culture Collection (ATCC) and authenticated by short tandem repeat profiling.

Techniques: Control, Liquid Chromatography with Mass Spectroscopy, Data-independent acquisition

Journal: Neoplasia (New York, N.Y.)

Article Title: Metabolic regulation of histone acetylation by ACLY supports MDR1 expression in colorectal cancer and highlights a targetable vulnerability

doi: 10.1016/j.neo.2026.101314

Figure Lengend Snippet: Metabolic and epigenetic consequences of vitamin C treatment in colorectal cancer cells. (A) Quantification of ¹³C-glucose-derived citrate in SW480 and DLD1 cells treated with vitamin C (5 mM) for 4 h (n = 3). (B) Immunoblot analysis of total ACLY and phosphorylated ACLY at Ser455 following vitamin C treatment (5 mM) (n = 3). (C) Immunoblot analysis and quantification of acetylated histone H4 (AcH4K16) and histone H3 (AcH3K9) in SW480 and DLD1 cells after vitamin C exposure (n = 3). (D) MDR1 (ABCB1) protein levels in SW480 and DLD1 cells treated with vitamin C (5 mM), quantified relative to vehicle control (n = 3). (E) Relative ACLY and ABCB1 mRNA expression determined by qPCR after 6 h of vitamin C treatment (5 mM) in SW480 and DLD1 cells (n = 3). Data are presented as mean ± SEM. Statistical significance was determined using unpaired two-tailed t-tests. *P < 0.05; **P < 0.01; ***P < 0.001.

Article Snippet: Human colorectal cancer cell lines SW480 (KRASG12V) and DLD1 (KRASG13D) were obtained from the American Type Culture Collection (ATCC) and authenticated by short tandem repeat profiling.

Techniques: Derivative Assay, Western Blot, Control, Expressing, Two Tailed Test

Journal: Genes & Diseases

Article Title: Blockade of co-inhibitory receptor immune checkpoint protein TIM3/CD366 augments the anti-cancer activity of CAR-T therapy in solid tumors: An ovarian cancer example

doi: 10.1016/j.gendis.2025.101978

Figure Lengend Snippet: Specific IFN-γ and TNF-α release of T lymphocytes transduced with TIM-3-silenced HER2-specific chimeric antigen receptor (CAR) or HER2-specific CAR. (A, B) TIM-3-silenced CAR-T cells and control T cells were co-incubated with Galectin-9 + or Galectin-9 – SKOV3 tumor cells (E:T ratio 5:1 or 10:1). At 20 h after coculture, a specific enzyme-linked immunosorbent assay was used to analyze the supernatant for IFN-γ cytokine-release. Results were presented as mean ± standard deviation. (C, D) The detection of TNF-α in the same culture supernatant. Results were presented as mean ± standard deviation. ∗ P < 0.05 and ∗∗ P < 0.01.

Article Snippet: Human cervical cancer cell line HeLa, lentivirus packaging cell line HEK 293TD, and human ovarian cancer cell line SKOV3 were purchased from American Type Culture Collection (Manassas, Virginia, USA) and cultured in Dulbecco's modified Eagle's medium (Invitrogen, Grand Island, New York) supplemented with 10% heat-inactivated fetal bovine serum.

Techniques: Transduction, Control, Incubation, Enzyme-linked Immunosorbent Assay, Standard Deviation

Journal: Genes & Diseases

Article Title: Blockade of co-inhibitory receptor immune checkpoint protein TIM3/CD366 augments the anti-cancer activity of CAR-T therapy in solid tumors: An ovarian cancer example

doi: 10.1016/j.gendis.2025.101978

Figure Lengend Snippet: TIM-3 silencing augmented the anti-tumor activity of chimeric antigen receptor-T (CAR-T) cells in vivo . 2 × 10 6 SKOV3 tumor cells expressing luciferase were intraperitoneally inoculated in a xenograft mouse model, and 7 days after inoculation, the 2 × 10 6 HER2-specific CAR-T kdTim-3 cells or CAR-T cells, or untreated T cells were intraperitoneally administered. (A, B) Tumor growth was monitored using an in vivo imaging system. (C) Survival curve of 80-day post-treatment. ∗ P < 0.05 and ∗∗ P < 0.01.

Article Snippet: Human cervical cancer cell line HeLa, lentivirus packaging cell line HEK 293TD, and human ovarian cancer cell line SKOV3 were purchased from American Type Culture Collection (Manassas, Virginia, USA) and cultured in Dulbecco's modified Eagle's medium (Invitrogen, Grand Island, New York) supplemented with 10% heat-inactivated fetal bovine serum.

Techniques: Activity Assay, In Vivo, Expressing, Luciferase, In Vivo Imaging

Journal: Translational Oncology

Article Title: Integrating spatial and single-cell transcriptomics via machine learning to characterize efferocytosis in hepatocellular carcinoma prognosis and immunotherapy

doi: 10.1016/j.tranon.2026.102801

Figure Lengend Snippet: Identification and multi-level validation of TPI1 as a pivotal prognostic driver. (A) Lollipop chart showing the selection frequency of feature genes across 101 machine learning models, identifying TPI1 as a high-frequency core gene. (B) Univariate Cox regression analysis of candidate genes; TPI1 exhibited the most substantial Hazard Ratio (HR), characterizing it as a preeminent risk factor. (C) Expression profiling of TPI1 across malignant versus paracancerous tissues within the TCGA-LIHC discovery cohort (upper) and GSE14520 validation cohort (lower). (D) Kaplan-Meier overall survival curves comparing patients with high and low TPI1 expression in the TCGA-LIHC (top) and GSE14520 (bottom) cohorts. (E) Relative mRNA expression levels of TPI1 in the immortalized human hepatocyte line (MIHA) and HCC cell lines (Huh7, SMMC-7721) determined by RT-qPCR. (F) Representative Western blot images (left) and densitometric quantification (right) of TPI1 protein levels in MIHA, Huh7, and SMMC-7721 cells. GAPDH served as the internal loading control. Data are expressed as mean ± SD. ** P < 0.01, *** P < 0.001.

Article Snippet: The human HCC cell lines (Huh7 and SMMC-7721) and the immortalized human hepatocyte line MIHA were procured from Procell Life Science & Technology Co., Ltd. (Wuhan, China).

Techniques: Biomarker Discovery, Selection, Expressing, Quantitative RT-PCR, Western Blot, Control