Analysis of miRNA profile in Ago2-IP fraction after miR-195 or miR-497 overexpression
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ABSTRACT: To explore functionally crucial tumor-suppressive (TS)-miRNAs in hepatocellular carcinoma (HCC), we performed integrative function- and expression-based screenings of TS-miRNAs in six HCC cell lines. The screenings identified seven miRNAs, which showed growth-suppressive activities through the overexpression of each miRNA and were endogenously downregulated in HCC cell lines. Further expression analyses using a large panel of HCC cell lines and primary tumors demonstrated four miRNAs, miR-101, -195, -378 and -497, as candidate TS-miRNAs frequently silenced in HCCs. Among them, two clustered miRNAs miR-195 and miR-497 showed significant growth-suppressive activity with induction of G1 arrest. Comprehensive exploration of their targets using Argonute2-immunoprecipitation-deep-sequencing (Ago2-IP-seq) and genome-wide expression profiling after their overexpression, successfully identified a set of cell-cycle regulators, including CCNE1, CDC25A, CCND3, CDK4, and BTRC. Our results suggest the molecular pathway regulating cell cycle progression to be integrally altered by downregulation of miR-195 and miR-497 expression, leading to aberrant cell proliferation in hepatocarcinogenesis. Analysis of miRNA profile change in the Ago2-IP fraction after overexpression with miR-195 or miR-497
ORGANISM(S): Homo sapiens
PROVIDER: GSE41079 | GEO | 2013/05/31
SECONDARY ACCESSION(S): PRJNA175703
REPOSITORIES: GEO
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