Adenomatous polyposis coli (APC) regulates miR17-92 cluster through ?-catenin pathway in colorectal cancer.

ABSTRACT: Adenomatous polyposis coli (APC) mutation is the most common genetic change in sporadic colorectal cancer (CRC). Although deregulations of miRNAs have been frequently reported in this malignancy, APC-regulated miRNAs have not been extensively documented. Here, by using an APC-inducible cell line and array analysis, we identified a total of 26 deregulated miRNAs. Among them, members of miR-17-92 cluster were dramatically inhibited by APC and induced by enforced expression of ?-catenin. Furthermore, we demonstrate that activated ?-catenin resulted from APC loss binds to and activates the miR-17-92 promoter. Notably, enforced expression of miR-19a overrides APC tumor suppressor activity, and knockdown of miR-19a in cancer cells with compromised APC function reduced their aggressive features in vitro. Finally, we observed that expression of miR-19a significantly correlates with ?-catenin levels in colorectal cancer specimens, and it is associated to the aggressive stage of tumor progression. Thus, our study reveals that miR-17-92 cluster is directly regulated by APC/?-catenin pathway and could be a potential therapeutic target in colon cancers with aberrant APC/?-catenin signaling.

SUBMITTER: Li Y 

PROVIDER: S-EPMC4960006 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature