Cancer Management and Research (Apr 2020)
microRNA-519d Induces Autophagy and Apoptosis of Human Hepatocellular Carcinoma Cells Through Activation of the AMPK Signaling Pathway via Rab10
Abstract
Yi-Jie Zhang,1,2 Qi Pan,1,2 Yang Yu,1,2 Xin-Ping Zhong1,2 1Department of Hepatobiliary and Organ Transplantation, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 2The Key Laboratory of Organ Transplantation of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of ChinaCorrespondence: Xin-Ping ZhongDepartment of Hepatobiliary and Organ Transplantation, The First Affiliated Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang 110001, Liaoning Province, People’s Republic of ChinaTel +86-13309831481Email [email protected] and Aim: Hepatocellular carcinoma (HCC) is a type of cancer with high mortality rates. The overexpression of microRNA-519d (miR-519d) has been explored in different types of cancers, which could significantly help suppress cancer development. This study aimed to investigate the interaction of miR-519d with its target gene, Rab10, as well as its effects on cell proliferation and autophagy in HCC cells through modulation of the AMPK signaling pathway.Methods: Microarray analysis was used to analyze the differentially expressed genes in HCC, and the target genes of the screened-out miRNA were predicted and verified. The expression of miR-519d and Rab10, AMPK signaling pathway-related proteins, apoptosis- and autophagy-related proteins was determined by RT-qPCR and Western blot analysis in HCC tissues and cell lines. Lastly, the effects of miR-519d and Rab10 in HCC cell proliferation, apoptosis, and mouse tumour xenograft in vivo were examined through gain- and loss-of-function experiments.Results: MiR-519d was down-regulated and Rab10 was upregulated in HCC tissues and cell lines. Overexpression of miR-519d decreased the expression of Rab10, mTOR, and Bcl-2, but increased the expression of Bax, Beclin1, Atg5, and p53. Upregulated miR-519d and downregulated Rab10 expression suppressed cell proliferation and induced cell apoptosis and autophagy in HCC cells. Finally, upregulation of miR-519d inhibited tumour growth in vivo.Conclusion: The result obtained in this study indicates that up-regulation of miR-519d inhibits proliferation and promotes apoptosis and autophagy of HCC cells through activation of the AMPK signaling pathway via downregulating Rab10, which provides a potential target for the treatment of HCC.Keywords: microRNA-519, Rab10, Adenosine 5ʹ-monophosphate-activated protein signaling pathway, hepatocellular carcinoma, proliferation, autophagy
