Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 85, Issue -, Pages 472-478Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2016.11.053
Keywords
Hepatocellular carcinoma; miR-98; EZH2; Wnt/beta-catenin pathway
Funding
- Science and Technology Research Project of Henan Province (International Science and Technology Cooperation Project) [162102410092]
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Hepatocellular carcinoma (HCC) is a highly aggressive solid malignancy in the word. Aberrant microRNA (miRNA) expression is involved in human diseases including cancer. In the current study, we explore the function of miR-98 in HCC cell proliferation. We found that expression level of miR-98 was significantly decreased in HCC tissues and cells lines compared with adjacent non-tumor issues and human hepatic cell line LO2. Increased expression of miR-98 suppressed HCC cell proliferation and arrested HCC cell cycle in G0/G1 phase. While, suppressed expression of miR-98 showed the opposite effect. Bioinformatics analysis revealed EZH2, a putative tumor promoter as a potential target of miR-98. Additionally, luciferase reporter assay revealed that miR-98 directly binds to the 3'-untranslated region (3'-UTR) of EZH2 mRNA. Furthermore, we demonstrated that miR-98 could reduce the Wnt/beta-catenin signal pathway by suppressing EZH2 directly. Moreover, inhibition of EZH2 abrogated the effect of miR-98 inhibitor on HCC cell proliferation. Taken together, these results suggested that miR-98 functioned as a potential tumor suppressor by regulating Wnt/beta-catenin signal pathway through direct suppression of EZH2 expression and might sever as a potential therapeutic target for HCC patients. (C) 2016 Elsevier Masson SAS. All rights reserved.
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