Dataset Information

Ubiquitin-speci?c protease 4 promotes metastasis of hepatocellular carcinoma by increasing TGF-? signaling-induced epithelial-mesenchymal transition.

ABSTRACT: Invasion and metastasis are the main cause of recurrence and death in advanced hepatocellular carcinoma (HCC). Revealing the mechanisms of HCC metastasis is important for developing new therapeutic approaches and reducing patient mortality. Ubiquitin specific protease 4 (USP4), is involved in tumorigenesis by deubiquitinating some important oncogenic proteins and impacting their degradation. In the present study, we found that USP4 was significantly upregulated in HCC tumor tissues and the high expression of USP4 was associated with distant metastasis and poor survival in patients. Using gene interference, we demonstrated that USP4 knockdown significantly inhibited HCC cell migration and invasion in vitro, and USP4 overexpression had the opposite results. In vivo, we also found that USP4 knockdown obviously blocked HCC cell metastasis. Mechanistically, we revealed that USP4 interacted directly with and deubiquitinated TGF-? receptor type I (TGFR-1) to activate the TGF-? signaling pathway, and subsequently induced the Epithelial-Mesenchymal Transition (EMT) in HCC cells. Taken together, our results elucidate that USP4 is highly expressed in HCC and promotes the tumor invasion and metastasis, the underlying mechanism is that USP4 directly interacts with and deubiquitinates TGFR-1 to increase TGF-? signaling-Induced EMT. These results could provide a new therapeutic target for the treatment of HCC.

SUBMITTER: Qiu C

PROVIDER: S-EPMC6224254 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Ubiquitin-speciﬁc protease 4 promotes metastasis of hepatocellular carcinoma by increasing TGF-β signaling-induced epithelial-mesenchymal transition.

Qiu Chan C Liu Yan Y Mei Ying Y Zou Min M Zhao Zhibo Z Ye Mingxin M Wu Xiaoling X

Aging 20181001 10

Invasion and metastasis are the main cause of recurrence and death in advanced hepatocellular carcinoma (HCC). Revealing the mechanisms of HCC metastasis is important for developing new therapeutic approaches and reducing patient mortality. Ubiquitin specific protease 4 (USP4), is involved in tumorigenesis by deubiquitinating some important oncogenic proteins and impacting their degradation. In the present study, we found that USP4 was significantly upregulated in HCC tumor tissues and the high ...[more]

PMID: 30335615

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Project description:BackgroundMetastatic bladder cancer (BLCA) is a lethal disease with an unmet need for study. Transgelin (TAGLN) is an actin-binding protein that affects the dynamics of the actin cytoskeleton indicating its robust potential as a metastasis initiator. Here, we sought to explore the expression pattern of TAGLN and elucidate its specific functioning and mechanisms in BLCA.MethodsA comprehensive assessment of TAGLN expression in BLCA was performed in three cohorts with a total of 847 patients. The potential effects of TAGLN on BLCA were further determined using clinical genomic analyses that guided the subsequent functional and mechanistic studies. In vitro migration, invasion assays and in vivo metastatic mouse model were performed to explore the biological functions of TAGLN in BLCA cells. Immunofluorescence, western blot and correlation analysis were used to investigate the molecular mechanisms of TAGLN.FindingsTAGLN was highly expressed in BLCA and correlated with advanced prognostic features. TAGLN promoted cell colony formation and cell migration and invasion both in vitro and in vivo by inducing invadopodia formation and epithelial-mesenchymal transition, during which a significant correlation between TAGLN and Slug was observed. The progression-dependent correlation between TGF-β and TAGLN was analysed at both the cellular and tissue levels, while TGF-β-mediated migration was abolished by the suppression of TAGLN.InterpretationOverall, TAGLN is a promising novel prognosis biomarker of BLCA, and its metastatic mechanisms indicate that TAGLN may represent a novel target agent that can be utilized for the clinical management of invasive and metastatic BLCA. FUND: This work was supported by the National Natural Science Foundation of China [81772703, 81672546, 81602253]; the Natural Science Foundation of Beijing [71772219, 7152146]. and Innovative Fund for Doctoral Students of Peking University Health Science Center (BUM2018BSS002). Funders had no role in the design of the study, data collection, data analysis, interpretation, or the writing of this report.

Dataset Information

Ubiquitin-speci?c protease 4 promotes metastasis of hepatocellular carcinoma by increasing TGF-? signaling-induced epithelial-mesenchymal transition.

Publications

Ubiquitin-speciﬁc protease 4 promotes metastasis of hepatocellular carcinoma by increasing TGF-β signaling-induced epithelial-mesenchymal transition.

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