title: MicroRNA-30b Suppresses Epithelial-Mesenchymal Transition and Metastasis of Hepatoma Cells.
abstract: Epithelial-mesenchymal transition (EMT) is critical for induction of invasiveness and metastasis in HCC. Growing evidence indicates that upregulation of Snail, the major EMT inducer, significantly correlates with the metastasis and poor prognosis of HCC. Here, we investigate the underlying mechanism of miR-30b in suppressing metastasis of hepatoma cells by targeting Snail. In this study, we found that miR-30b was significantly downregulated and negatively associated with Snail production in HCC cell lines with higher metastatic potentials. Gain- and loss-of-function studies revealed that miR-30b could dramatically inhibit in vitro HCC cell migration and invasion. In vivo orthotopic liver xenograft model further demonstrated that stable over-expression of miR-30b significantly repressed the local invasion and lung metastasis of hepatoma cells. Meanwhile, the restoration of miR-30b expression suppressed the distant colonization of hepatoma cells. Both gain- and loss-of-function studies showed that miR-30b suppressed the EMT of hepatoma cells as indicated by the morphology changes and deregulation of epithelial and mesenchymal markers. Using RNAi, we further investigated the role of Snail in HCC cell EMT and demonstrated that knockdown of Snail significantly inhibited the EMT and cancer cell metastasis. Additionally, miR-30b exhibited inhibitory effects on HCC cell proliferation in vitro and in vivo. In conclusion, our findings highlight the significance of miR-30b downregulation in HCC tumor metastasis and invasiveness, and implicate a new potential therapeutic target for HCC metastasis. J. Cell. Physiol. 232: 625-634, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.
authors.forename: Huanan
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.
authors.forename: Hanwen
authors.initials: H
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.
authors.forename: Jiangning
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Zang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.|Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, Nanjing, PR China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D000071250:Snail Family Transcription Factors / Q000378:metabolism
chemical_list: C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D000071250:Snail Family Transcription Factors