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

• Published in: PloS one Vol. 11; no. 6; p. e0158432
• Main Authors: Hu, Tanyu, Phiwpan, Krung, Guo, Jitao, Zhang, Wei, Guo, Jie, Zhang, Zhongmei, Zou, Mangge, Zhang, Xuejie, Zhang, Jianhua, Zhou, Xuyu
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.06.2016; Public Library of Science (PLoS)
• Subjects: 3' Untranslated Regions; Adenomatous polyposis coli; Analysis; Animals; Base Sequence; beta Catenin - genetics; beta Catenin - metabolism; Binding Sites; Biology and life sciences; Cancer; Cell cycle; Cell Line; Cell Proliferation; Cloning; Deoxyribonucleic acid; Discordance; DNA; Gene expression; Gene Expression Regulation; Homeostasis; Humans; Immunology; Laboratories; Life sciences; Lymphocytes; Medical research; Medicine and Health Sciences; Mice; MicroRNA; MicroRNAs; MicroRNAs - chemistry; MicroRNAs - genetics; miRNA; mRNA; Mutagenesis; Nucleic Acid Conformation; Plasmids; Polyposis coli; Protein Biosynthesis - genetics; Regulators; Ribonucleic acid; RNA; Signal transduction; Signaling; Stem cells; Wnt protein; Wnt proteins; Wnt Proteins - metabolism; Wnt Signaling Pathway; β-Catenin; Beijing China; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0158432

Wnt/β-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/β-catenin signaling by using a TopFlash based luciferase reporter. Surprisingly, we found that miR-142 inhibited Wnt/β-catenin signaling, which was inconsistent with a recent study showing that miR-142-3p targeted Adenomatous Polyposis Coli (APC) to upregulate Wnt/β-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/β-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 β-catenin) through binding to its 3' untranslated region (3' UTR). Finally, miR-142 was able to repress cell cycle progression by inhibiting active Wnt/β-catenin signaling. Thus, our findings highlight the inhibitory role of miR-142-3p in Wnt/β-catenin signaling, which help to understand the complex regulation of Wnt/β-catenin signaling.