MiR-20a induces cell radioresistance by activating PTEN/PI3K/AKT signaling pathways in hepatocellular carcinoma
Menée sur des lignées cellulaires de carcinome hépatocellulaire, cette étude met en évidence un mécanisme par lequel le micro-ARN miR-20a induit une radiorésistance des cellules tumorales en activant la voie de signalisation PTEN/PI3K/AKT
Purpose : This study was undertaken to investigate the role of miR-20a in hepatocellular carcinoma (HCC) cell radioresistance, which may reveal potential strategies to improve treatment. Methods and Materials : The expression of miR-20a and PTEN were detected in HCC cell lines and paired primary tissues by qRT-PCR. Cell radiation combined with colony formation assays were administrated to discover the effect of miR-20a on radiosensitivity. Bioinformatics prediction and luciferase assay were used to identify the target of miR-20a. The kinase inhibitor LY294002 was used to inhibit Akt to investigate whether miR-20a affects HCC cell radioresistance through activating the PTEN/PI3k/Akt pathway. Results : MiR-20a levels were increased in HCC cell lines and tissueswhile PTEN was inversely correlated with it. Overexpression of miR-20a in Bel-7402 and SMMC-7721 cells enhances their resistance to the effect of ionizing radiation and that inhibition of miR-20a in HCCLM3 and QGY-7701 cells sensitizes them to it. Phosphatase and tensin (PTEN) gene was identified as a direct functional target of miR-20a for the induction of radioresistance. Overexpression of miR-20a activated the PTEN/PI3K/AKT signaling pathway. Additionally, the kinase inhibitor LY294002 could reverse the effect of miR-20a-induced radioresistance. Conclusion : MiR-20a induces HCC cells radioresistance by activating PTEN/PI3K/AKT pathway which suggested that miR-20a/PTEN/PI3K/AKT might represent a target of investigation for developing effective therapeutic strategies against HCC.
http://www.redjournal.org/article/S0360-3016(15)00405-8/abstract