Cancer Management and Research (Oct 2020)
Overexpression of Rab40b Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis via PI3K/AKT Signaling Pathway
Abstract
Li-Wei Shi,1,2 Zhi-Bo Zhao,3 Li Zhong,1 Jian Gao,1 Jian-Ping Gong,3 Hang Chen,4 Yu Min,4 Yi-Yin Zhang,5 Zhi Li4 1Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 2Department of Gastroenterology, Chongqing People’s Hospital, Chongqing 400010, People’s Republic of China; 3Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 4Department of Breast & Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 5Department of Anesthesiology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 401120, People’s Republic of ChinaCorrespondence: Zhi LiDepartment of Breast & Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing 400010, People’s Republic of ChinaTel +86 18883147602Email [email protected]: Rab40b is an evolutionarily conserved Rab GTPase that plays an important role in intracellular trafficking and is closely related to cancer progression. However, the role and potential molecular mechanism of Rab40b in hepatocellular carcinoma (HCC) have not yet been elucidated.Materials and Methods: The expression of Rab40b in HCC tissues and peritumour tissues was tested by qRT-PCR, Western blotting and histological analysis. A Kaplan–Meier survival curve was generated based on the expression of Rab40b in the HCC samples. Cell proliferation assays, wound healing assays, and transwell assays are used to examine the effect of Rab40b on HCC cell growth in vitro. The effect of Rab40b on cell cycle was examined by flow cytometry. A xenograft implantation model was used to assess the effect of Rab40b on the development of HCC cells in vivo.Results: Rab40b protein expression is upregulated in HCC tissues, and this upregulation is associated with high pathological stage and poor prognosis in HCC patients. Rab40b overexpression promotes the proliferation and metastasis of HCC cells by upregulating cyclin D1, cyclin E1 and matrix metalloproteinase 2 (MMP2) through the PI3K/AKT signalling pathway. Conversely, Rab40b inhibitors can significantly inhibit the proliferation and metastasis of HCC cell lines and induce G0/G1 cell cycle arrest and apoptosis. Studies of a nude mouse xenograft model demonstrated that Rab40b knockdown can significantly inhibit the proliferation and progression of HCC tumours in vivo.Conclusion: Overall, this study demonstrates that Rab40b is an important oncoprotein that promotes HCC progression by regulating the expression of cyclin D1, cyclin E1, p21 and MMP2 through the PI3K/AKT signalling pathway.Keywords: Rab40b, HCC, cell cycle, PI3K/AKT, cyclins, MMP2
