title: Over-expression of miR-106b promotes cell migration and metastasis in hepatocellular carcinoma by activating epithelial-mesenchymal transition process.
abstract: Hepatocellular carcinoma (HCC) is one the the most fatal cancers worldwide. The poor prognosis of HCC is mainly due to the developement of distance metastasis. To investigate the mechanism of metastasis in HCC, an orthotopic HCC metastasis animal model was established. Two sets of primary liver tumor cell lines and corresponding lung metastasis cell lines were generated. In vitro functional analysis demonstrated that the metastatic cell line had higher invasion and migration ability when compared with the primary liver tumor cell line. These cell lines were subjected to microRNA (miRNAs) microarray analysis to identify differentially expressed miRNAs which were associated with the developement of metastasis in vivo. Fifteen human miRNAs, including miR-106b, were differentially expressed in 2 metastatic cell lines compared with the primary tumor cell lines. The clinical significance of miR-106b in 99 HCC clinical samples was studied. The results demonstrated that miR-106b was over-expressed in HCC tumor tissue compared with adjacent non-tumor tissue (p = 0.0005), and overexpression of miR-106b was signficantly correlated with higher tumor grade (p = 0.018). Further functional studies demonstrated that miR-106b could promote cell migration and stress fiber formation by over-expressing RhoGTPases, RhoA and RhoC. In vivo functional studies also showed that over-expression of miR-106b promoted HCC metastasis. These effects were related to the activation of the epithelial-mesenchymal transition (EMT) process. Our results suggested that miR-106b expression contributed to HCC metastasis by activating the EMT process promoting cell migration in vitro and metastasis in vivo.
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. robertap@hku.hk
authors.forename: Wing Lung
authors.initials: WL
authors.lastname: Yau
authors.forename: Colin Siu Chi
authors.initials: CS
authors.lastname: Lam
authors.forename: Lui
authors.initials: L
authors.lastname: Ng
authors.forename: Ariel Ka Man
authors.initials: AK
authors.lastname: Chow
authors.forename: Sylvia Tsz Ching
authors.initials: ST
authors.lastname: Chan
authors.forename: Jacky Yu Ki
authors.initials: JY
authors.lastname: Chan
authors.forename: Jana Yim Hung
authors.initials: JY
authors.lastname: Wo
authors.forename: Kevin Tak Pan
authors.initials: KT
authors.lastname: Ng
authors.forename: Kwan
authors.initials: K
authors.lastname: Man
authors.forename: Ronnie Tung Ping
authors.initials: RT
authors.lastname: Poon
authors.forename: Roberta Wen Chi
authors.initials: RW
authors.lastname: Pang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003599:Cytoskeleton / Q000378:metabolism; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D008297:Male; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C542541:MIRN106 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D020741:rho GTP-Binding Proteins