title: miR-490-3p modulates cell growth and epithelial to mesenchymal transition of hepatocellular carcinoma cells by targeting endoplasmic reticulum-Golgi intermediate compartment protein 3 (ERGIC3).
abstract: MicroRNAs (miRNAs) are considered to be regulators of various biological processes in cancers, including the epithelial to mesenchymal transition (EMT), which is a key factor in cancer metastasis. In this study, we aimed to clarify the potential roles of miR-490-3p in hepatocellular carcinoma (HCC) cells. Using real-time quantitative RT-PCR, we discovered that miR-490-3p was up-regulated in HCC tissues and cells compared with the adjacent non-tumor tissues and normal cells. We also found that overexpression of miR-490-3p led to an increase in cell proliferation, migration, and invasion abilities and that it contributed to EMT. The inhibition of miR-490-3p had the opposite effect on the cells. We identified ERGIC3 (endoplasmic reticulum-Golgi intermediate compartment protein 3) as a direct target gene for miR-490-3p. Unlike most miRNA-mRNA interactions, miR-490-3p increased ERGIC3 mRNA and protein levels as well as the intensity of expression of the EGFP reporter gene controlled by the 3'-UTR of ERGIC3 mRNA. The up-regulation by miR-490-3p also required the participation of Ago2. The inhibition of miR-490-3p reduced the expression of ERGIC3. Overexpression of ERGIC3 led to the same effect on HCC cells as miR-490-3p overexpression, including EMT. Importantly, silencing ERGIC3 reversed the cellular responses mediated by miR-490-3p overexpression. In conclusion, our study indicated for the first time that miR-490-3p functioned like an oncogenic miRNA in HCC cells and that the inhibition of miR-490-3p might provide an potential treatment approach for HCC patients.
authors.affiliation: Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, No. 22 Qi-Xiang-Tai Road, Tianjin 300070, China.
authors.forename: Ling-yun
authors.initials: LY
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; C517615:ERGIC3 protein, human; C574862:MIRN490 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm