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miR‐29b Regulates Intestinal Epithelium Homeostasis by Modulating Wnt Co‐receptor LRP6 Translation
Author(s) -
Li Yanwu,
Liu Lan,
Rao Jaladanki,
Zou Tongtong,
Xiao Lan,
Chang Hee Kyoung,
Gorospe Myriam,
Wang JianYing
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.851.1
Subject(s) - wnt signaling pathway , lrp6 , messenger rna , gene silencing , transfection , microbiology and biotechnology , repressor , microrna , translation (biology) , biology , antagomir , chemistry , signal transduction , gene expression , biochemistry , gene
microRNAs regulate gene expression at the post‐transcription level and are implicated in many aspects of cellular physiology. Our previous study shows that microRNA‐29b (miR‐29b) acts as a biological repressor of intestinal mucosal growth, but its exact down‐stream targets remain largely unknown. This study tested the hypothesis that miR‐29b inhibits intestinal mucosal growth by altering Wnt‐signaling activity through modulation of Wnt co‐receptor LRP6 (LDL receptor‐related protein 6) expression. Methods: Studies were conducted in Caco‐2 cells, and miR‐29b function was examined by its ectopic overexpression and silencing. Results: The LRP6 mRNA was a novel target of miR‐29b since it directly bound to the miR‐29b as measured by biotinylated RNA pull‐down assays. Increased [miR‐29b/LRP6 mRNA] association by transfection with the miR‐29b precursor decreased the rate of newly LRP6 protein synthesis but did not affect the stability of LRP6 mRNA as shown by its half‐life, whereas miR‐29b silencing by transfection with the antagomir targeting miR‐29b increased LRP6 translation. LRP6 translation was also inhibited by miR‐29b through a process involving RNA‐binding protein HuR (a potent enhancer of LRP6 translation), since miR‐29b also interacted with and repressed HuR mRNA translation. Conclusions These data indicate that miR‐29b inactivates Wnt‐signaling by inhibiting LRP6 translation, thus down‐regulating intestinal epithelial renewal.