p53 regulates nuclear GSK-3 levels through miR-34-mediated Axin2 suppression in colorectal cancer cells.

摘要: p53 is a bona fide tumor suppressor gene whose loss of function marks the most common genetic alteration in human malignancy. Although causal link between and tumorigenesis has been clearly demonstrated, mechanistic links by which potentiates oncogenic signaling are not fully understood. Recent evidence indicates that microRNA-34 (miR-34) family, transcriptional target p53, directly suppresses set canonical Wnt genes Snail, resulting p53-mediated suppression EMT process. In this study, we report regulates GSK-3β nuclear localization via miR-34-mediated Axin2 colorectal cancer. Exogenous miR-34a decreases UTR-reporter activity through multiple binding sites within 5' 3' UTR Axin2. Suppression or miR-34 increases abundance leads to decreased Snail expression cancer cells. Conversely, non-coding causes depletion endogenous miR-sponge effect together with increased function, supporting RNA-RNA interactions transcripts act as an decoy for miR-34. Further, RNA were correlated clinical data patients. biological relevance GSK-3 level studied, our results demonstrate p53/miR-34 axis plays role regulating levels