Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs.

ABSTRACT: Acquired resistance to cancer drug therapies almost always occurs in advanced-stage patients even following a significant response to treatment. In addition to mutational mechanisms, various non-mutational resistance mechanisms have now been recognized. We previously described a chromatin-mediated subpopulation of reversibly drug-tolerant persisters that is dynamically maintained within a wide variety of tumour cell populations. Here we explore a potential role for microRNAs in such transient drug tolerance. Functional screening of 879 human microRNAs reveals miR-371-3p as a potent suppressor of drug tolerance. We identify PRDX6 (peroxiredoxin 6) as a key target of miR-371-3p in establishing drug tolerance by regulating PLA2/PKCα activity and reactive oxygen species. PRDX6 expression is as

SUBMITTER: Sahu N 

PROVIDER: S-EPMC4976141 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature