Journal: Genetics and Molecular Biology

Article Title: Identification of potential target genes of USP22 via ChIP-seq and RNA-seq analysis in HeLa cells

doi: 10.1590/1678-4685-gmb-2017-0164

Figure Lengend Snippet: Figure 4 - Knockdown of UPS22 by siRNA modulates gene expression in HeLa cells. (A and B) Western blot analysis of USP22 silencing in HeLa cells. (C) Pie charts show the ratio of up-regulated or down-regulated genes by UPS22 silencing in HeLa cells. (D) Quantitative RT-PCR analysis of the relative levels of mRNA transcripts of some genes targeted by UPS22. Data are expressed as the mean SD of each group of genes and the levels of mRNA tran- scripts in the control siRNA-transfected cells were designated as 100. Data are representative of three independent experiments.

Article Snippet: HeLa cells were infected with USP22-specific shRNA lentiviral particles (sc-63195-V, Santa Cruz Biotechnology) or control shRNA lentiviral particles (sc-108080, Santa Cruz Biotechnology), following the manufacturer’s recommendations.

Techniques: Knockdown, Gene Expression, Western Blot, Quantitative RT-PCR, Control, Transfection

Journal: Translational cancer research

Article Title: Biological effects of ubiquitin-specific peptidase 22 on thyroid papillary cancer cells and its mechanism of action.

doi: 10.21037/tcr-20-2102

Figure Lengend Snippet: Figure 1 The protein level of USP22 in TPC-1 cells was higher than that in HT-ori 3 normal thyroid epithelial cells. USP22, ubiquitin-

Article Snippet: The following primary antibodies were purchased: β-actin monoclonal antibody (60008-1-Ig, Proteintech in America), USP22 polyclonal antibody (LS-C99567, LifeSpace in Australia); Bmi-1 polyclonal antibody (ab126783, Abcam in England); and cyclin D2 polyclonal antibody (TA323121, Origene Company in America).

Techniques: Ubiquitin Proteomics

Journal: Translational cancer research

Article Title: Biological effects of ubiquitin-specific peptidase 22 on thyroid papillary cancer cells and its mechanism of action.

doi: 10.21037/tcr-20-2102

Figure Lengend Snippet: Figure 3 USP22 mRNA expression in the USP22-siRNA1 TPC-

Article Snippet: The following primary antibodies were purchased: β-actin monoclonal antibody (60008-1-Ig, Proteintech in America), USP22 polyclonal antibody (LS-C99567, LifeSpace in Australia); Bmi-1 polyclonal antibody (ab126783, Abcam in England); and cyclin D2 polyclonal antibody (TA323121, Origene Company in America).

Techniques: Expressing

Journal: Translational cancer research

Article Title: Biological effects of ubiquitin-specific peptidase 22 on thyroid papillary cancer cells and its mechanism of action.

doi: 10.21037/tcr-20-2102

Figure Lengend Snippet: Figure 4 In the USP22 siRNA1 group, the migrative number of TPC-1 cells within 6 h of gene silencing decreased compared with that

Article Snippet: The following primary antibodies were purchased: β-actin monoclonal antibody (60008-1-Ig, Proteintech in America), USP22 polyclonal antibody (LS-C99567, LifeSpace in Australia); Bmi-1 polyclonal antibody (ab126783, Abcam in England); and cyclin D2 polyclonal antibody (TA323121, Origene Company in America).

Techniques:

Journal: Translational cancer research

Article Title: Biological effects of ubiquitin-specific peptidase 22 on thyroid papillary cancer cells and its mechanism of action.

doi: 10.21037/tcr-20-2102

Figure Lengend Snippet: Figure 5 The number of invasive TPC-1 cells in USP22 siRNA1 group decreased in 24 h compared with that in negative control group and

Article Snippet: The following primary antibodies were purchased: β-actin monoclonal antibody (60008-1-Ig, Proteintech in America), USP22 polyclonal antibody (LS-C99567, LifeSpace in Australia); Bmi-1 polyclonal antibody (ab126783, Abcam in England); and cyclin D2 polyclonal antibody (TA323121, Origene Company in America).

Techniques: Negative Control

Journal: Translational cancer research

Article Title: Biological effects of ubiquitin-specific peptidase 22 on thyroid papillary cancer cells and its mechanism of action.

doi: 10.21037/tcr-20-2102

Figure Lengend Snippet: Figure 6 MTT assay. OD570 value of TPC-1 cells in USP22-

Article Snippet: The following primary antibodies were purchased: β-actin monoclonal antibody (60008-1-Ig, Proteintech in America), USP22 polyclonal antibody (LS-C99567, LifeSpace in Australia); Bmi-1 polyclonal antibody (ab126783, Abcam in England); and cyclin D2 polyclonal antibody (TA323121, Origene Company in America).

Techniques: MTT Assay

Journal: Translational cancer research

Article Title: Biological effects of ubiquitin-specific peptidase 22 on thyroid papillary cancer cells and its mechanism of action.

doi: 10.21037/tcr-20-2102

Figure Lengend Snippet: Figure 7 The number of TPC-1 cell clones formed in the USP22-

Article Snippet: The following primary antibodies were purchased: β-actin monoclonal antibody (60008-1-Ig, Proteintech in America), USP22 polyclonal antibody (LS-C99567, LifeSpace in Australia); Bmi-1 polyclonal antibody (ab126783, Abcam in England); and cyclin D2 polyclonal antibody (TA323121, Origene Company in America).

Techniques: Clone Assay

Journal: Translational cancer research

Article Title: Biological effects of ubiquitin-specific peptidase 22 on thyroid papillary cancer cells and its mechanism of action.

doi: 10.21037/tcr-20-2102

Figure Lengend Snippet: Figure 8 The protein levels of USP22, Bmi-1 and cyclinD2 of TPC-1 cells in the USP22-siRNA1 group decreased compared with the

Article Snippet: The following primary antibodies were purchased: β-actin monoclonal antibody (60008-1-Ig, Proteintech in America), USP22 polyclonal antibody (LS-C99567, LifeSpace in Australia); Bmi-1 polyclonal antibody (ab126783, Abcam in England); and cyclin D2 polyclonal antibody (TA323121, Origene Company in America).

Techniques:

Journal: Translational cancer research

Article Title: Biological effects of ubiquitin-specific peptidase 22 on thyroid papillary cancer cells and its mechanism of action.

doi: 10.21037/tcr-20-2102

Figure Lengend Snippet: Figure 10 USP22 mRNA expression of the USP22-siRNA1 HT-

Article Snippet: The following primary antibodies were purchased: β-actin monoclonal antibody (60008-1-Ig, Proteintech in America), USP22 polyclonal antibody (LS-C99567, LifeSpace in Australia); Bmi-1 polyclonal antibody (ab126783, Abcam in England); and cyclin D2 polyclonal antibody (TA323121, Origene Company in America).

Techniques: Expressing

Journal: Translational cancer research

Article Title: Biological effects of ubiquitin-specific peptidase 22 on thyroid papillary cancer cells and its mechanism of action.

doi: 10.21037/tcr-20-2102

Figure Lengend Snippet: Figure 11 OD570 value of HT-ori 3 cells in USP22-siRNA1 group

Article Snippet: The following primary antibodies were purchased: β-actin monoclonal antibody (60008-1-Ig, Proteintech in America), USP22 polyclonal antibody (LS-C99567, LifeSpace in Australia); Bmi-1 polyclonal antibody (ab126783, Abcam in England); and cyclin D2 polyclonal antibody (TA323121, Origene Company in America).

Techniques:

Journal: The FEBS journal

Article Title: Deubiquitinating enzymes regulate Hes1 stability and neuronal differentiation.

doi: 10.1111/febs.13290

Figure Lengend Snippet: Fig. 2. Interactions of Usp27x and its deletion mutants with Hes1. (A) Schematic representation of Usp27x and its mutants, showing the region to which Hes1 binds. Usp27x has a catalytic USP domain. Hes1 binds to the region between signatures 1 and 2 (asterisks) in the USP domain. n.d., not detected. (B) Co- immunoprecipitation of Hes1 with Usp27x deletion mutants. HA- tagged Hes1 was co-transfected with FLAG-tagged Usp27x and its deletion mutants into HEK293T cells; their interactions were then analyzed by immunoprecipitation with FLAG antibody and western blotting using FLAG and HA antibodies. (C) Sequence alignment of Usp27x homologs. Part of the phylogenetic tree generated by ClustalW [39] from all deubiquitinases in mouse, with their identity scores relative to Usp27x in parentheses (%). (D) Schematic representation of the domains in Usp27x, Usp22 and Usp51. ZF, zinc finger.

Article Snippet: Measurement of Hes1 protein and mRNA For protein analysis, each sample was lysed in lysis buffer (0.5% Nonidet P-40 (Nacalai Tesque, Kyoto, Japan), 100 mM NaCl, 5 mM MgCl2, 10 mM imidazole, 50 mM Tris/HCl, pH 8.0) at the time points indicated in figures, and 10–20 lg total protein at each time point was analyzed by western blotting with Hes1 antibody (1:2000; a kind gift from Tetsuo Sudo, TORAY Industries Inc., Tokyo, Japan), Usp22 antibody (1:2000; Novus Biologicals, Littleton, CO, USA) and actin antibody (1:2000; Sigma); actin was used as a loading control.

Techniques: Immunoprecipitation, Transfection, Western Blot, Sequencing, Generated

Journal: The FEBS journal

Article Title: Deubiquitinating enzymes regulate Hes1 stability and neuronal differentiation.

doi: 10.1111/febs.13290

Figure Lengend Snippet: Fig. 3. Usp27x and its homologs stabilize Hes1 protein. (A) Usp27x stabilizes Hes1. HA-tagged Hes1 was co-transfected with FLAG-tagged Usp27x or its derivatives into C3H10T1/2 cells. Hes1 stability was analyzed by a cycloheximide (CHX) chase assays. Protein levels were analyzed by western blotting with HA antibody (upper panels), and the relative amounts of Hes1 were quantified (lower panel). (B,C) Usp27x homologs stabilize Hes1. HA-tagged Hes1 was co-transfected with FLAG-tagged Usp51, Usp3, Usp22 or Usp22 mutants into C3H10T1/2 cells. Hes1 degradation was analyzed as in (A). (D–G) Usp27x, Usp22, Usp51 and Usp3 knockdown. C3H10T1/2 cells were transfected with control, or siRNAs specific to Usp27x (D), Usp22 (E), Usp51 (F) or Usp3 (G). Protein levels were analyzed by western blotting with Hes1 and actin antibodies, and quantified. The relative amounts of Hes1 were normalized against the amounts of actin. The half-life of Hes1 protein was estimated from exponential curves fitted using Kaleidagraph software. (H) Estimated copy numbers of Usp22, Usp27x and Usp51. The copy numbers of Usp22, Usp27x and Usp51 mRNA in 50 ng total RNA of C3H10T1/2 cells were determined by quantitative PCR with known amounts of plasmids encoding these factors. Values are means SEM from two independent experiments. Asterisks indicate statistically significant differences (*P < 0.05, **P < 0.01; Student’s t test).

Article Snippet: Measurement of Hes1 protein and mRNA For protein analysis, each sample was lysed in lysis buffer (0.5% Nonidet P-40 (Nacalai Tesque, Kyoto, Japan), 100 mM NaCl, 5 mM MgCl2, 10 mM imidazole, 50 mM Tris/HCl, pH 8.0) at the time points indicated in figures, and 10–20 lg total protein at each time point was analyzed by western blotting with Hes1 antibody (1:2000; a kind gift from Tetsuo Sudo, TORAY Industries Inc., Tokyo, Japan), Usp22 antibody (1:2000; Novus Biologicals, Littleton, CO, USA) and actin antibody (1:2000; Sigma); actin was used as a loading control.

Techniques: Transfection, Western Blot, Knockdown, Control, Software, Real-time Polymerase Chain Reaction

Journal: The FEBS journal

Article Title: Deubiquitinating enzymes regulate Hes1 stability and neuronal differentiation.

doi: 10.1111/febs.13290

Figure Lengend Snippet: Fig. 4. Effect of Usp22 knockdown on Hes1 oscillation. (A,B). Hes1 oscillation was induced by serum stimulation in C3H10T1/2 cells. Levels of Hes1 mRNA (A) and Hes1 and Usp22 proteins (B) were measured every 30 min after serum stimulation by quantitative PCR and western blotting, respectively. Values are means SEM of four (A) and three (B) independent experiments. Asterisks indicate statistically significant differences (**P < 0.01, ***P < 0.001; Student’s t test and two-way ANOVA). (C) Representative blots of Usp22, Hes1 and actin. There are two bands for Hes1 protein because of modification. The knockdown efficiency of Usp22 mRNA was 96.2%.

Article Snippet: Measurement of Hes1 protein and mRNA For protein analysis, each sample was lysed in lysis buffer (0.5% Nonidet P-40 (Nacalai Tesque, Kyoto, Japan), 100 mM NaCl, 5 mM MgCl2, 10 mM imidazole, 50 mM Tris/HCl, pH 8.0) at the time points indicated in figures, and 10–20 lg total protein at each time point was analyzed by western blotting with Hes1 antibody (1:2000; a kind gift from Tetsuo Sudo, TORAY Industries Inc., Tokyo, Japan), Usp22 antibody (1:2000; Novus Biologicals, Littleton, CO, USA) and actin antibody (1:2000; Sigma); actin was used as a loading control.

Techniques: Knockdown, Real-time Polymerase Chain Reaction, Western Blot

Journal: The FEBS journal

Article Title: Deubiquitinating enzymes regulate Hes1 stability and neuronal differentiation.

doi: 10.1111/febs.13290

Figure Lengend Snippet: Fig. 6. Usp27x and Usp22 repress neuronal differentiation in the developing brain. (A,B) Usp22 knockdown in neural stem cells. Control siRNA or Usp22 siRNA were electroporated with the nuclear-localizing GFP vector into the neocortex of E13.5 mouse embryos in the same mother uterus, and harvested at E15.5. Sections were stained with GFP antibody (green), TUJ-1 antibody (red) and 40,6-diamidino-2- phenylindole (DAPI) (blue). (C,D) Mis-expression of Usp27x in neural stem cells. Control vector or Usp27x expression vector were electroporated as described in (A). Boxed regions in (A) and (C) are enlarged in (B) and (D), respectively. White lines in (B) and (D) indicate the surface of the ventricle. Scale bars = 100 lm. (E) Quantification of cell distribution, showing the percentage of GFP-positive cells in various cortical layers (CP, cortical plate; IZ, intermediate zone; MZ, marginal zone; SVZ, sub-ventricular zone; VZ, ventricular zone). Values are means SEM from four independent experiments. Asterisks indicate statistically significant differences (***P < 0.001, **P < 0.01; Student’s t test). Two embryos and at least two sections from each embryo were analyzed for each independent experiment. (F) Expression of Hes1, Usp22 and Usp27x in the developing brain. In situ hybridization of Hes1, Usp22 and Usp27x in sagittal brain sections of E13.5 mouse embryo. Sections were hybridized with dioxygenin-labeled antisense RNA probes, and stained using the nitro blue tetrazolium 5-bromo-4-chloro-3- indolyl-phosphate detection system as described previously [28]. Sequence information for the RNA probes is available upon request.

Article Snippet: Measurement of Hes1 protein and mRNA For protein analysis, each sample was lysed in lysis buffer (0.5% Nonidet P-40 (Nacalai Tesque, Kyoto, Japan), 100 mM NaCl, 5 mM MgCl2, 10 mM imidazole, 50 mM Tris/HCl, pH 8.0) at the time points indicated in figures, and 10–20 lg total protein at each time point was analyzed by western blotting with Hes1 antibody (1:2000; a kind gift from Tetsuo Sudo, TORAY Industries Inc., Tokyo, Japan), Usp22 antibody (1:2000; Novus Biologicals, Littleton, CO, USA) and actin antibody (1:2000; Sigma); actin was used as a loading control.

Techniques: Knockdown, Control, Plasmid Preparation, Staining, Expressing, In Situ Hybridization, Labeling, Sequencing

Journal: MedComm

Article Title: Ubiquitin‐specific protease 22 promotes tumorigenesis and progression by an FKBP12/mTORC1/autophagy positive feedback loop in hepatocellular carcinoma

doi: 10.1002/mco2.439

Figure Lengend Snippet: Usp22 accelerates c‐Myc/NrasGV12‐induced hepatocarcinogenesis. (A) Study design (created with BioRender.com). C57BL/6J mice were grouped as G1, G2, G3, and G4. (B) Survival curves of G1 ( n = 7) and G2 ( n = 9). Usp22 overexpression shortened the survival time of mice ( p = 0.0239). (C) Survival curves of G3 ( n = 5) and G4 ( n = 6). Usp22 ablation prolongs the survival time of mice ( p = 0.0018). (D) Representative images of gross liver specimens, hematoxylin–eosin (HE), Flag‐tag, and Ki‐67 staining in the G1 and G2 groups. (E) Representative images of gross liver specimens, HE, and Ki‐67 staining in the G3 and G4 groups. (F) The weight of livers in each group ( * p < 0.05).

Article Snippet: Usp22 conditional knockout mice were purchased from Cyagen Biosciences.

Techniques: Over Expression, FLAG-tag, Staining

Journal: MedComm

Article Title: Ubiquitin‐specific protease 22 promotes tumorigenesis and progression by an FKBP12/mTORC1/autophagy positive feedback loop in hepatocellular carcinoma

doi: 10.1002/mco2.439

Figure Lengend Snippet: USP22 overexpression activates the mTORC1 pathway. (A) Heatmap of differentially expressed genes (DEGs) in Huh‐7 oeNC and oeUSP22 cells based on RNA sequencing data. (B) Volcano plots of DEGs in two cell lines. (C) The changes in key molecules in the mTORC1 pathway following USP22 overexpression are shown in the heatmap. (D) Gene set enrichment analysis (GSEA) revealed the activated mTORC1 pathway in the Huh‐7 oeUSP22 cells compared to oeNC cells (|normalized enrichment score| ≥ 1, p < 0.05, false discovery rate < 0.25). (E) Western blot results showing the key proteins of the mTORC1 pathway in Huh‐7 cells. (F) Western blot results showing the key proteins of the mTORC1 pathway in Hep‐3B cells. (G) Western blot results showing protein expression in c‐Myc/NrasGV12‐induced hepatocellular carcinoma tissues of mice with or without Usp22 overexpression. (H) Western blot results showing protein expressions in c‐Myc/NrasGV12‐induced tumor tissues of Usp22 fl/fl ; Alb‐Cre or Usp22 fl/fl mice. β‐Actin was used as a loading control.

Article Snippet: Usp22 conditional knockout mice were purchased from Cyagen Biosciences.

Techniques: Over Expression, RNA Sequencing, Western Blot, Expressing, Control

Journal: MedComm

Article Title: Ubiquitin‐specific protease 22 promotes tumorigenesis and progression by an FKBP12/mTORC1/autophagy positive feedback loop in hepatocellular carcinoma

doi: 10.1002/mco2.439

Figure Lengend Snippet: USP22 exerts tumor‐promoting functions and drives rapamycin sensitivity in hepatocellular carcinoma cells. (A) The effects of USP22 knockdown or overexpression on cell proliferation in Huh‐7 and Hep‐3B cells detected using a cell counting kit‐8 (CCK‐8) assay ( n = 4). (B) The sensitivities of USP22 knockdown or overexpression cells toward rapamycin assessed in Huh‐7 and Hep‐3B cells using a CCK‐8 assay ( n = 4). (C) Variations in rapamycin sensitivity detected by trypan blue staining‐based cell counts ( n = 3). (D) Colony formation results and rapamycin sensitivity variations of Huh‐7 and Hep‐3B cells after USP22 knockdown or overexpression visualized by crystal violet staining. (E) The corresponding quantization diagrams of (D) ( n = 3). (F) Migratory properties and variations in rapamycin sensitivity of Huh‐7 and Hep‐3B cells after USP22 knockdown or overexpression visualized by crystal violet staining. (G) The corresponding quantization diagrams of (F) ( n = 3) ( * p < 0.05, ** p < 0.01, *** p < 0.001).

Article Snippet: Usp22 conditional knockout mice were purchased from Cyagen Biosciences.

Techniques: Knockdown, Over Expression, Cell Counting, CCK-8 Assay, Staining

Journal: MedComm

Article Title: Ubiquitin‐specific protease 22 promotes tumorigenesis and progression by an FKBP12/mTORC1/autophagy positive feedback loop in hepatocellular carcinoma

doi: 10.1002/mco2.439

Figure Lengend Snippet: USP22 promotes tumor growth and sensitivity to rapamycin in vivo. (A) The tumor images of each group ( n = 5). (B) Tumor volumes measured and compared every 4 days in each group. (C) The calculated relative tumor volume (Rapa/vehicle). Compared to the oeNC group, significant tumor regression was observed in the oeUSP22 group ( p < 0.01). (D) Tumor weights of each group. (E) Mouse body weights of each group. There are no significant differences noted. (F) Hematoxylin–eosin staining and USP22 expression in two patient‐derived tumor xenograft models in the F0 and F6 generations. (G) Tumor images of each group ( n = 5). (H) Tumor volumes of each group. (I) Comparison of the relative tumor volume (Rapa/vehicle). (J) Tumor weights of each group. (K) Mouse body weights of each group, there are no significant differences noted ( * p < 0.05, ** p < 0.01, *** p < 0.001).

Article Snippet: Usp22 conditional knockout mice were purchased from Cyagen Biosciences.

Techniques: In Vivo, Staining, Expressing, Derivative Assay, Comparison

Journal: MedComm

Article Title: Ubiquitin‐specific protease 22 promotes tumorigenesis and progression by an FKBP12/mTORC1/autophagy positive feedback loop in hepatocellular carcinoma

doi: 10.1002/mco2.439

Figure Lengend Snippet: The effect of USP22 on FKBP12 protein stabilization and ubiquitination. (A) The change in FKBP12 protein in Hep‐3B and Huh‐7 cells. (B) Silencing of FKBP12 downregulated the proteins of the mTORC1 pathway in Hep‐3B cells. (C) Elevated p‐p70S6K (T389) in oeUSP22 cells could be rescued by additional silencing of FKBP12. (D) Isolated extracts from HEK293T cells obtained for immunoprecipitation (IP) using either an anti‐Myc or anti‐Flag antibody. (E) IP assay results of endogenous USP22 and FKBP12 in SNU‐449 cells. (F) Co‐localization of FKBP12 (green) with USP22 (red) observed using confocal microscopy and indicated by yellow arrow. (G) Illustration of USP22 and its point mutants. (H) HEK293T cells transfected with FKBP12‐Flag plasmids along with NC, Myc‐USP22 (wt), and each of the point mutants. (I) Western blot and ImageJ results in Hep‐3B shUSP22 or shNC cells after cycloheximide treatment (50 μg/mL). (J) Western blot and ImageJ results in SNU‐449 oeUSP22 or oeNC cells after cycloheximide treatment (50 μg/mL). (K) Western blot showing changes in FKBP12 after MG132 (10 μM, 2 h) or 3‐methyladenine (3‐MA) (5 mM, 12 h) treatment. (L) The ubiquitination of FKBP12 using IP and western blotting in Hep‐3B shUSP22 cells. (M) The ubiquitination of FKBP12 using IP and western blotting in HEK‐293T cells with USP22 overexpression.

Article Snippet: Usp22 conditional knockout mice were purchased from Cyagen Biosciences.

Techniques: Ubiquitin Proteomics, Isolation, Immunoprecipitation, Confocal Microscopy, Transfection, Western Blot, Over Expression

Journal: MedComm

Article Title: Ubiquitin‐specific protease 22 promotes tumorigenesis and progression by an FKBP12/mTORC1/autophagy positive feedback loop in hepatocellular carcinoma

doi: 10.1002/mco2.439

Figure Lengend Snippet: Activated mTORC1 stabilizes USP22 by inhibiting autophagic degradation. (A) Activated mTORC1 mediated by si‐tuberous sclerosis 1 (TSC1) stabilized USP22 protein level, and further rapamycin treatment diminished the upregulated USP22 and simultaneously activated autophagy in hepatocellular carcinoma cells. (B) Reduced protein level of USP22 with rapamycin treatment could be reversed by additional inhibition of autophagy (si‐Beclin‐1). (C) The autophagosome formations observed by transmission electron microscopy (yellow arrows). (D) Hep‐3B cells with or without knockdown of TSC1 transfected with mRFP‐GFP‐LC3 plasmid, and then treated with or without rapamycin. Yellow puncta represent autophagosomes and red puncta represent autolysosomes.

Article Snippet: Usp22 conditional knockout mice were purchased from Cyagen Biosciences.

Techniques: Inhibition, Transmission Assay, Electron Microscopy, Knockdown, Transfection, Plasmid Preparation

Journal: MedComm

Article Title: Ubiquitin‐specific protease 22 promotes tumorigenesis and progression by an FKBP12/mTORC1/autophagy positive feedback loop in hepatocellular carcinoma

doi: 10.1002/mco2.439

Figure Lengend Snippet: Clinical significance of USP22 in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). (A) Different expression levels of USP22 and FKBP12 detected using immunohistochemical staining in two LT recipients diagnosed with HCC. (B) Positive correlation between USP22 and FKBP12 expression in 205 HCC tissues ( R 2 = 0.3609, p < 0.0001). (C) The effect of USP22 on the overall survival (OS) of LT recipients with HCC exceeding the Milan Criteria evaluated using the Kaplan–Meier method ( n = 115, p = 0.027). (D) The effect of sirolimus (SRL) on the OS of recipients with high USP22 expression assessed using the Kaplan–Meier method ( n = 68, p = 0.012). (E) The effect of SRL on the OS of recipients with low USP22 expression shown using the Kaplan–Meier method ( n = 47, p = 0.465). (F) Diagram of the molecular mechanisms of USP22, FKBP12, mTORC1, and autophagy in HCC.

Article Snippet: Usp22 conditional knockout mice were purchased from Cyagen Biosciences.

Techniques: Transplantation Assay, Expressing, Immunohistochemical staining, Staining