title: MicroRNA-30d promotes tumor invasion and metastasis by targeting Galphai2 in hepatocellular carcinoma.
abstract: The pathological relevance and significance of microRNAs (miRNAs) in hepatocarcinogenesis have attracted much attention in recent years; however, little is known about the underlying molecular mechanisms through which miRNAs are involved in the development and progression of hepatocellular carcinoma (HCC). In this study, we demonstrate that miR-30d is frequently up-regulated in HCC and that its expression is highly associated with the intrahepatic metastasis of HCC. Furthermore, the enhanced expression of miR-30d could promote HCC cell migration and invasion in vitro and intrahepatic and distal pulmonary metastasis in vivo, while silencing its expression resulted in a reduced migration and invasion. Galphai2 (GNAI2) was identified as the direct and functional target of miR-30d with integrated bioinformatics analysis and messenger RNA array assay. This regulation was further confirmed by luciferase reporter assays. In addition, our results, for the first time, showed that GNAI2 was frequently suppressed in HCC by way of quantitative reverse-transcription polymerase chain reaction and immunohistochemical staining assays. The increase of the GNAI2 expression significantly inhibits, whereas knockdown of the GNAI2 expression remarkably enhances HCC cell migration and invasion, indicating that GNAI2 functions as a metastasis suppressor in HCC. The restoration of GNAI2 can inhibit miR-30d-induced HCC cell invasion and metastasis.
  
  
  CONCLUSIONS
  The newly identified miR-30d/GNAI2 axis elucidates the molecular mechanism of HCC cell invasion and metastasis and represents a new potential therapeutic target for HCC treatment.
authors.affiliation: Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yao
authors.forename: Linhui
authors.initials: L
authors.lastname: Liang
authors.forename: Shenglin
authors.initials: S
authors.lastname: Huang
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.forename: Ning
authors.initials: N
authors.lastname: Tan
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Mingxia
authors.initials: M
authors.lastname: Yan
authors.forename: Chao
authors.initials: C
authors.lastname: Ge
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Taoyang
authors.initials: T
authors.lastname: Chen
authors.forename: Dafang
authors.initials: D
authors.lastname: Wan
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Jinjun
authors.initials: J
authors.lastname: Li
authors.forename: Jianren
authors.initials: J
authors.lastname: Gu
authors.forename: Xianghuo
authors.initials: X
authors.lastname: He
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000556:secondary; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured
chemical_list: C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D051960:GTP-Binding Protein alpha Subunit, Gi2