Search

Objectives: Integrin beta‐like 1 (ITGBL1) is involved in the migration and invasion of several cancers; however, its roles in the development and progression of hepatocellular carcinoma (HCC) remain largely unknown. Materials and methods: Immunohistochemistry staining was used to investigate the expression pattern of ITGBL1 and its prognostic values in HCC patients. The transwell, wound‐healing assays, xenograft and orthotopic mouse models were employed to determine the effects of ITGBL1 on HCC cell migration and invasion in vitro and in vivo. The biological mechanisms involved in cell migration and invasion caused by ITGBL1 were determined with Western blotting and RT‐PCR methods. Results: ITGBL1 expression was significantly increased in HCC tissues compared to adjacent normal tissues. Patients with higher ITGBL1 expression were associated with more reduced overall survival. ITGBL1 overexpression promoted migration and invasion in SMMC‐7721 and HepG2 cells in vitro and in vivo, whereas knockdown or knockout ITGBL1 in CSQT‐2 cells significantly reduced cell migration and invasion abilities. In SMMC‐7721 cells, ITGBL1 overexpression stimulated TGF‐β/Smads signalling pathway, along with the KRT17 and genes involved in the epithelial‐mesenchymal transition (EMT). In contrast, ITGBL1 knockout inhibited the TGF‐β/Smads signalling pathway in CSQT‐2 cells. Conclusions: These findings suggested that ITGBL1 promoted migration and invasion in HCC cells by stimulating the TGF‐β/Smads signalling pathway. ITGBL1 could be a promising prognostic biomarker, as well as a potential therapeutic target in HCC. [ABSTRACT FROM AUTHOR]

Patients receiving sorafenib treatment for hepatocellular carcinoma (HCC) experience different treatment efficacy. Personalized sorafenib treatment should be achieved through the identification of predictors of therapeutic response. In the current study, we found that high UGT1A9 expression indicated better prognosis for HCC patients treated with sorafenib after surgery. In silico analysis predicted microRNA-200a/-183 as potential regulators of the UGT1A gene family via binding to the shared UGT1A9 3'-UTR. A significant inverse correlation between microRNA-200a/-183 and UGT1A9 mRNA level was observed in a panel of HCC specimens. Direct binding was further demonstrated by luciferase reporter gene vector carrying wild-type or binding site truncated UGT1A9 3'-UTR. MicroRNA-200a/-183 downregulated UGT1A9 expression in a dose-dependent manner and significantly reduced sorafenib β-D-glucuronide formation in HCC cells. These data indicated that UGT1A9, under epigenetic regulation of microRNA-200a/-183, could predict patients who might benefit from adjuvant sorafenib treatment after surgery. [ABSTRACT FROM AUTHOR]