title: Control of mitogenic and motogenic pathways by miR-198, diminishing hepatoma cell growth and migration.
abstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths, worldwide. MicroRNAs, inhibiting gene expression by targeting various transcripts, are involved in genomic dysregulation during hepatocellular tumorigenesis. In previous studies, microRNA-198 (miR-198) was shown to be significantly downregulated in HCV-positive hepatocellular carcinoma (HCC). Herein, the function of miR-198 in hepatocellular carcinoma cell growth and gene expression was studied. In hepatoma cell-types with low levels of liver-specific transcription factor HNF1α indicating a low differentiation grade, miR-198 expression was most downregulated. However, miR-198 treatment did not restore the expression of the liver-specific transcription factors HNF1α or HNF4α. Importantly, overexpression of miR-198 in Pop10 hepatoma cells markedly reduced cell growth. In agreement, comprehensive gene expression profiling by microarray hybridisation and real-time quantification revealed that central signal transducers of proliferation pathways were downregulated by miR-198. In contrast, genes mediating cellular adherence were highly upregulated by miR-198. Thus, the low expression of E-cadherin and claudin-1, involved in cell adhesion and cell-cell contacts, was abolished in hepatoma cells after miR-198 overexpression. This definite induction of both proteins by miR-198 was shown to be accompanied by a significantly impaired migration activity of hepatoma Pop10 cells. In conclusion, miR-198 acts as a tumor suppressor by repression of mitogenic and motogenic pathways diminishing cell growth and migration.
authors: Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors: Natalia
authors: N
authors: Elfimova
authors: Elisabeth
authors: E
authors: Sievers
authors: Hannah
authors: H
authors: Eischeid
authors: Monika
authors: M
authors: Kwiecinski
authors: Andrea
authors: A
authors: Noetel
authors: Heike
authors: H
authors: Hunt
authors: Diana
authors: D
authors: Becker
authors: Peter
authors: P
authors: Frommolt
authors: Maria
authors: M
authors: Quasdorff
authors: Hans Michael
authors: HM
authors: Steffen
authors: Peter
authors: P
authors: Nürnberg
authors: Reinhard
authors: R
authors: Büttner
authors: Andreas
authors: A
authors: Teufel
authors: Hans-Peter
authors: HP
authors: Dienes
authors: Uta
authors: U
authors: Drebber
authors: Margarete
authors: M
authors: Odenthal
mesh_terms: D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D062445:Claudin-1 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D062445:Claudin-1; C496487:HNF1A protein, human; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; C535221:MIRN198 microRNA, human; D035683:MicroRNAs