miR-1247-5p functions as a tumor suppressor in human hepatocellular carcinoma by targeting Wnt3

Chu,Yuankui; Fan,Weining; Guo,Wenwei; Zhang,Yixin; Wang,Lixin; Guo,Le; Duan,Xiangguo; Wei,Jun; Xu,Guangxian

doi:10.3892/or.2017.5702

miR-1247-5p functions as a tumor suppressor in human hepatocellular carcinoma by targeting Wnt3

Authors:
- Yuankui Chu
- Weining Fan
- Wenwei Guo
- Yixin Zhang
- Lixin Wang
- Le Guo
- Xiangguo Duan
- Jun Wei
- Guangxian Xu
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Affiliations: Medical Experimental Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Department of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
Published online on: June 6, 2017 https://doi.org/10.3892/or.2017.5702
Pages: 343-351

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Abstract

Increasing evidence suggests that aberrant expression of certain microRNAs (miRNAs) may participate in the genesis and progression of tumors. Several studies have indicated that miR-1247-5p plays different roles in various types of cancer cells. The effects of miR-1247-5p on human hepatocellular carcinoma (HCC) cells are elusive. In the present study, we investigated the effects of miR-1247-5p on the progression of HCC. The transcript of miR-1247-5p was markedly downregulated in clinical samples of patients with HCC and HCC cell lines, and ectopic overexpression of miR‑1247-5p markedly inhibited the proliferation and invasion of HepG2 cells, induced cell apoptosis in vitro, and suppressed the growth of transplanted tumors in vivo. Wnt3 was found to be a potential target of miR-1247-5p and overexpression of miR-1247-5p was able to significantly downregulate the expression of Wnt3 by directly targeting the 3'UTR of this gene, which was verified by luciferase reporter assay and western blotting. Furthermore, we found that the miR-1247-5p gene was hypermethylated in HepG2 cells, and the transcript of miR-1247-5p was increased significantly after treatment with the demethylation drug 5-azacytidine. These findings demonstrated that miR-1247-5p functions as a tumor suppressor in human HCC by targeting Wnt3 and that the expression of miR-1247-5p can be regulated by DNA methylation, which indicates that miR-1247-5p has the potential to be a therapeutic target as well as a diagnostic marker of HCC.

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