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microRNA-519d Induces Autophagy and Apoptosis of Human Hepatocellular Carcinoma Cells Through Activation of the AMPK Signaling Pathway via Rab10

Authors Zhang YJ, Pan Q, Yu Y, Zhong XP

Received 4 March 2019

Accepted for publication 9 December 2019

Published 15 April 2020 Volume 2020:12 Pages 2589—2602

DOI https://doi.org/10.2147/CMAR.S207548

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Ahmet Emre Eskazan


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 China

Correspondence: Xin-Ping Zhong
Department 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 China
Tel +86-13309831481
Email zhongxp2@yeah.net

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.

Keywords: microRNA-519, Rab10, Adenosine 5ʹ-monophosphate-activated protein signaling pathway, hepatocellular carcinoma, proliferation, autophagy

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