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miR-1-3p suppresses proliferation of hepatocellular carcinoma through targeting SOX9

Authors Zhang H, Zhang Z, Gao L, Qiao Z, Yu M, Yu B, Yang T

Received 6 December 2018

Accepted for publication 13 February 2019

Published 22 March 2019 Volume 2019:12 Pages 2149—2157

DOI https://doi.org/10.2147/OTT.S197326

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr William Cho


Hao Zhang,1,* Zhenya Zhang,2,* Lili Gao,3 Zhengdong Qiao,3 Minghua Yu,4 Bo Yu,1,3 Tao Yang1

1Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, People’s Republic of China; 2Department of General Surgery, Hebei Medical University Fourth Hospital, Shijiazhuang 050011, People’s Republic of China; 3Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, People’s Republic of China; 4Department of Medical Oncology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, People’s Republic of China

*These authors contributed equally to this work

Background: Liver cancer was the fourth leading cause of cancer-related death in 2015. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. miR-1-3p plays important roles in cancer, including prostate, bladder, lung cancer, and colorectal carcinoma. The function of miR-1-3p in HCC remains poorly understood.
Methods: qRT-PCR was performed to detect the miR-1-3p expression in HCC cell lines (HCCLM3, Hep3B, Bel-7404, SMMC-7721) and the normal human hepatic cell line (LO2). HCCLM3 and Bel-7404 cells were transfected with miR-1-3p mimic or scramble control followed by water-soluble tetrazolium salt (WST-1) assay. Western bolt analysis was performed to determine the protein levels. TargetScan7.1 (http://www.targetscan.org/vert_71/) was used to predict the potential targets of miR-1-3p. SRY (sex determining region Y)-box 9 (SOX9), which has been previously shown to play an important role in HCC, was found to be a target of miR-1-3p. Luciferase reporter assay was used to explore the targeting of miR-1-3p on SOX9. For in vivo tumorigenesis assay, HCCLM3 cells with stable overexpression of miR-1-3p or control plasmid were injected subcutaneously into the flank of the SCID mice and animals were monitored for tumor growth.
Results: miR-1-3p was significantly downregulated in HCC cell lines (HCCLM3, Hep3B, Bel-7404, and SMMC-7721) compared to normal human hepatic cell line (LO2). Overexpression of miR-1-3p significantly inhibited the proliferation and induced apoptosis in HCCLM3 and Bel-7474 cells. SOX9 was a direct target of miR-1-3p in HCC cells. Inhibition of SOX9 significantly inhibited the proliferation of HCCLM3 and Bel-7474 cells. In vivo, overexpression of miR-1-3p decreased tumor volume in a xenograft model.
Conclusion: These results highlight the role of miR-1-3p in HCC. Overexpression of miR-1-3P inhibited the proliferation of HCC at least partly due to the regulation of SOX9. miR-1-3p may be a promising therapeutic candidate for HCC.

Keywords: miR-1-3p, hepatocellular carcinoma, SOX9, proliferation, apoptosis

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