<p>microRNA-519d Induces Autophagy and Apoptosis of Human Hepatocellular Carcinoma Cells Through Activation of the AMPK Signaling Pathway via Rab10</p>
Authors: Yang Yu
Yi-Jie Zhang
Qi Pan
Xin-Ping Zhong
Journal: Cancer Management and Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: Adenosine 5ʹ-monophosphate-activated protein signaling pathway; Rab10; autophagy; hepatocellular carcinoma; microRNA-519
Affiliations: Department of Hepatobiliary and Organ Transplantation, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China., The Key Laboratory of Organ Transplantation of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.

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. 

Retracted: No

PubPeer comments:
 Figs 3E, 6E ( Cell cycle of Huh7 cells ). ![file] Were these images hand-drawn? , 
 Figs 3B, 6B. ![file] The LC3-I and LC3-II bands have quite different lane widths. This seems unusual. Western Blots in this distinctive style are often encountered in papers that also display curious hand-drawn cell-cycle plots as in #1. Sometimes they also include flow-cytometry scatterplots that resemble pineapples that are toppling over. Here, Figs 3F, 6F. ![file] , 
 I compiled this montage of Western Blots, sourced from various papers, each with its own PP thread. To my mind there is (as it were) a family kinship among them all, all sampling a small corner of  morphological space . Many other family members could be adduced. Clockwise from upper left: - [Wang et al (2020)] - [Gao et al (2021)] - [Chen et al (2020)] - [He et al (2021)] . ![file] In addition, WBs from [Lv et al (2020)] *[retracted]* ![] This may be my over-active imagination, but Figs 3B and 6B seem to fit into the same genre. Is it possible for the authors to upload or link to higher-resolution scans of the original blots, to dispel any concerns? ![] ,