title: miR-29b represses intestinal mucosal growth by inhibiting translation of cyclin-dependent kinase 2.
abstract: The epithelium of the intestinal mucosa is a rapidly self-renewing tissue in the body, and defects in the renewal process occur commonly in various disorders. microRNAs (miRNAs) posttranscriptionally regulate gene expression and are implicated in many aspects of cellular physiology. Here we investigate the role of miRNA-29b (miR-29b) in the regulation of normal intestinal mucosal growth and further validate its target mRNAs. miRNA expression profiling studies reveal that growth inhibition of the small intestinal mucosa is associated with increased expression of numerous miRNAs, including miR-29b. The simple systemic delivery of locked nucleic acid-modified, anti-miR-29b-reduced endogenous miR-29b levels in the small intestinal mucosa increases cyclin-dependent kinase 2 (CDK2) expression and stimulates mucosal growth. In contrast, overexpression of the miR-29b precursor in intestinal epithelial cells represses CDK2 expression and results in growth arrest in G1 phase. miR-29b represses CDK2 translation through direct interaction with the cdk2 mRNA via its 3'-untranslated region (3'-UTR), whereas point mutation of miR-29b binding site in the cdk2 3'-UTR prevents miR-29b-induced repression of CDK2 translation. These results indicate that miR-29b inhibits intestinal mucosal growth by repressing CDK2 translation.
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201 Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201 Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201 Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD 21224.
authors.forename: Lan
authors.initials: L
authors.lastname: Xiao
authors.forename: Jaladanki N
authors.initials: JN
authors.lastname: Rao
authors.forename: Tongtong
authors.initials: T
authors.lastname: Zou
authors.forename: Lan
authors.initials: L
authors.lastname: Liu
authors.forename: Shan
authors.initials: S
authors.lastname: Cao
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martindale
authors.forename: Weijie
authors.initials: W
authors.lastname: Su
authors.forename: Hee Kyoung
authors.initials: HK
authors.lastname: Chung
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007413:Intestinal Mucosa / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics*; D051381:Rats
chemical_list: C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2
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