<p>microRNA-519d Induces Autophagy and Apoptosis of Human Hepatocellular Carcinoma Cells Through Activation of the AMPK Signaling Pathway via Rab10</p>
Yijie Zhang, Qi Pan, Yang Yu, Xin-Ping Zhong
Abstract
BACKGROUND 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.