MicroRNA-493 suppresses cell proliferation and invasion by targeting ZFX in human hepatocellular carcinoma

Article type: Research Article

Authors: Ding, Wei^{a; b; 1} | Tan, Hongbo^{c; 1} | Li, Xuemei^a | Zhang, Yue^a | Fang, Fang^b | Tian, Yuanyuan^a | Li, Jin^a | Pan, Xinghua^{d; *}

Affiliations: [a] Department of Clinical Laboratory, Kunming General Hospital, Chinese People’s Liberation Army, Kunming 650032, Yunnan, China | [b] College of Medicine, Yunnan Economic Management College, Kunming 650106, Yunnan, China | [c] Department of Orthopedics, Kunming General Hospital of Chinese People’s Liberation Army, Kunming 650032, Yunnan, China | [d] Stem Cell Engineering Laboratory of Yunnan Province, Kunming General Hospital, Chinese People’s Liberation Army, Kunming 650032, Yunnan, China

Correspondence: [*] Corresponding author: Xinghua Pan, Stem Cell Engineering Laboratory of Yunnan Province, Kunming General Hospital, Chinese People’s Liberation Army, Daguan Road, Kunming 650032, Yunnan, China. Tel.: +86 871 64774488; Fax: +86 871 64774488; E-mail: pm52055266@163.com.

Note: [1] Co-first authors.

Abstract: BACKGROUNDS: MicroRNAs (miRNAs) are some RNA molecules that negatively regulate gene expression by binding to the 3’-untranslated region (3’-UTR) of target mRNA molecules. The aim of the study is to investigate the clinical role and functional effects of microRNA-493 (miR-493) in human hepatocellular carcinoma (HCC). METHODS: Expression of miR-493 in 58 cases of HCC tissues and adjacent normal tissues was determined by using quantitative real-time PCR (qRT-PCR) analyses. In vitro, cell proliferation and invasion capacity was evaluated by CCK8 assay and trans-well invasion assay. Luciferase reporter assay, western blot and qRT-PCR were used to detect the association between miR-493 expression and zinc finger protein X-linked (ZFX) in HCC. RESULTS: Expression of miR-493 was significantly downregulated in HCC tissues compared to adjacent normal tissues. Lower miR-493 expression associated with tumor size, vascular invasion and poor overall survival (OS) and disease free survival (DFS) time of HCC patients. In vitro, transfection of miR-493 mimic in HCC cells inhibited cell proliferation and invasion abilities. However, transfection of miR-493 inhibitor in HCC cells had promoting effects. Luciferase reporter assay, qRT-PCR and western blot analysis demonstrated that miR-493 targeting 3’-untranslated region (3’-UTR) of ZFX and overexpression of miR-493 inhibited its expression. Moreover, enforced ZFX expression rescued the effects of miR-493 mimic on cell proliferation and invasion. CONCLUSION: MiR-493 functioned as tumor suppressor in HCC cells by regulating ZFX expression. Thus, miR-493 may provide potential value for HCC treatment.

Keywords: MicroRNAs, miR-493, ZFX, cell proliferation, cell invasion

DOI: 10.3233/CBM-171036

Journal: Cancer Biomarkers, vol. 22, no. 3, pp. 427-434, 2018