miRNA-302b Suppresses Human Hepatocellular Carcinoma by Targeting AKT2

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en régulant l'expression du gène AKT2, le micro-ARN miR-302b joue un rôle de suppresseur de tumeurs dans les carcinomes hépatocellulaires

Résumé en anglais

miRNAs (miRs) play a critical role in human cancers including hepatocellular carcinoma (HCC). Although miR-302b has been suggested to function as a tumor repressor in other cancers, its role in HCC is unknown. This study investigated the expression and functional role of miR-302b in human HCC. The expression level of miR-302b is dramatically decreased in clinical HCC specimens, as compared to their respective non-neoplastic counterparts, and in HCC cell lines. Overexpression of miR-302b suppressed HCC cell proliferation and G1/S-transition in vitro, whereas inhibition of miR-302b promoted HCC cell proliferation and G1/S-transition. Using a luciferase reporter assay, AKT2 was determined to be a direct target of miR-302b. Subsequent investigation revealed that miR-302b expression was inversely correlated with AKT2 expression in HCC tissue samples. Importantly, silencing AKT2 recapitulated the cellular and molecular effects seen upon miR-302b overexpression, which included inhibiting HCC cell proliferation, suppressing G1 regulators (Cyclin A, Cyclin D1, CDK2) and increasing p27Kip1 phosphorylation at Ser10. Restoration of AKT2 counteracted the effects of miR-302b expression. Moreover, miR-302b was able to repress tumor growth of HCC cells in vivo. Implications: Taken together, miR-302b inhibits HCC cell proliferation and growth in vitro and in vivo by targeting AKT2.