MiR-34a chemosensitizes bladder cancer cells to cisplatin treatment regardless of p53-Rb pathway status.

ABSTRACT: MiR-34a is a downstream effector of p53 that has been shown to target several molecules associated with cell cycle and cell survival pathways. As alterations in these pathways are frequent in muscle invasive transitional cell carcinoma of the bladder (MI-TCC), for example mutation or loss of p53 and Rb, the goal of this study was to determine whether manipulation of miR-34a expression levels could abrogate the effect of these alterations and sensitize bladder cancer cells to chemotherapy. We demonstrate that transfection of T24, TCCSUP and 5637 with pre-miR-34a followed by cisplatin treatment results in a dramatic reduction in clonogenic potential and induction of senescence compared to treatment with cisplatin alone. Molecular analyses identified Cdk6 and sirtuin (SIRT)-1 as being targete

SUBMITTER: Vinall RL 

PROVIDER: S-EPMC4568996 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature