MicroRNA-142-3p Negatively Regulates Canonical Wnt Signaling Pathway.

ABSTRACT: Wnt/?-catenin signaling pathway plays essential roles in mammalian development and tissue homeostasis. MicroRNAs (miRNAs) are a class of regulators involved in modulating this pathway. In this study, we screened miRNAs regulating Wnt/?-catenin signaling by using a TopFlash based luciferase reporter. Surprisingly, we found that miR-142 inhibited Wnt/?-catenin signaling, which was inconsistent with a recent study showing that miR-142-3p targeted Adenomatous Polyposis Coli (APC) to upregulate Wnt/?-catenin signaling. Due to the discordance, we elaborated experiments by using extensive mutagenesis, which demonstrated that the stem-loop structure was important for miR-142 to efficiently suppress Wnt/?-catenin signaling. Moreover, the inhibitory effect of miR-142 relies on miR-142-3p rather than miR-142-5p. Further, we found that miR-142-3p directly modulated translation of Ctnnb1 mRNA (encoding ?-catenin) through binding to its 3' untranslated region (3' UTR). Finally, miR-142 was able to repress cell cycle progression by inhibiting active Wnt/?-catenin signaling. Thus, our findings highlight the inhibitory role of miR-142-3p in Wnt/?-catenin signaling, which help to understand the complex regulation of Wnt/?-catenin signaling.

SUBMITTER: Hu T 

PROVIDER: S-EPMC4922628 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature