title: MiR-195 is a key negative regulator of hepatocellular carcinoma metastasis by targeting FGF2 and VEGFA.
abstract: Hepatocellular carcinoma (HCC) is the most common primary tumor of liver and the fifth most common cancer in the world. Lung is the most frequent site for extra hepatic metastasis from hepatocellular carcinoma, while the cause and mechanism of it is still poor understood. Here, we identify that the expression of miR-195 is markedly impaired in the lung metastasis cell lines of HCC. The result of Real-time PCR reveals the expression of miR-195 is significantly downregulated in 92 HCC tissues. Low expression of miR-195 is associated with tumor size, portal vein thrombosis, TNM stage and patients survival. Luciferase reporter and ELISA assay prove that hematogenous metastasis related genes including FGF2 and VEGFA are the target genes of miR-195. Overexpression of miR-195 in HCC cell line BEL-7402 markedly inhibits the capability of migration and invasion. Taken together, our results suggest that miR-195, a tumor suppressor miRNA, contributes to the lung metastasis of HCC by negatively regulating FGF2 and VEGFA, providing key implications of miR-195 for the therapeutic intervention of HCC.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China; Department of General Surgery, People's Hospital of ZhengzhouZhengzhou 450003, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of General Surgery, People's Hospital of Zhengzhou Zhengzhou 450003, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, People's Hospital of Zhengzhou Zhengzhou 450003, China.
authors.forename: Linlong
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of General Surgery, People's Hospital of Zhengzhou Zhengzhou 450003, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, China.
authors.forename: Xinguang
authors.initials: X
authors.lastname: Qiu
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014162:Transfection; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C552722:MIRN195 microRNA, human; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2
keywords: FGF2; Hepatocellular carcinoma; VEGFA; metastasis; miR-195
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