title: miR-98 inhibits hepatocellular carcinoma cell proliferation via targeting EZH2 and suppressing Wnt/β-catenin signaling pathway.
abstract: 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/β-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/β-catenin signal pathway through direct suppression of EZH2 expression and might sever as a potential therapeutic target for HCC patients.
authors.affiliation: Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan Province, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan Province, China.
authors.forename: Jiang-Tao
authors.initials: JT
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan Province, China.
authors.forename: Long
authors.initials: L
authors.lastname: Hua
authors.affiliation: Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan Province, China.
authors.forename: Kun-Hou
authors.initials: KH
authors.lastname: Yao
authors.affiliation: Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan Province, China. Electronic address: hujunhong73@163.com.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Wang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; C546084:MIRN98 microRNA, human; D035683:MicroRNAs; D051153:Wnt Proteins; D051176:beta Catenin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
keywords: EZH2; Hepatocellular carcinoma; Wnt/β-catenin pathway; miR-98