title: MicroRNA-142-3p Negatively Regulates Canonical Wnt Signaling Pathway.
abstract: 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.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Tanyu
authors.initials: T
authors.lastname: Hu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.|Faculty of Allied Health Sciences, University of Phayao, 19 Moo 2 tambon Maeka Amphore Muang Phayao province, Thailand.
authors.forename: Krung
authors.initials: K
authors.lastname: Phiwpan
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Jitao
authors.initials: J
authors.lastname: Guo
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Guo
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Zhongmei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Mangge
authors.initials: M
authors.lastname: Zou
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Xuejie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Xuyu
authors.identifier: http://orcid.org/0000-0002-6626-0898
authors.initials: X
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis / Q000235:genetics; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C495267:CTNNB1 protein, mouse; D035683:MicroRNAs; C529102:Mirn142 microRNA, mouse; D051153:Wnt Proteins; D051176:beta Catenin