title: JunD enhances miR-29b levels transcriptionally and posttranscriptionally to inhibit proliferation of intestinal epithelial cells.
abstract: Through its actions as component of the activating protein-1 (AP-1) transcription factor, JunD potently represses cell proliferation. Here we report a novel function of JunD in the regulation of microRNA expression in intestinal epithelial cells (IECs). Ectopically expressed JunD specifically increased the expression of primary and mature forms of miR-29b, whereas JunD silencing inhibited miR-29b expression. JunD directly interacted with the miR-29b1 promoter via AP-1-binding sites, whereas mutation of AP-1 sites from the miR-29b1 promoter prevented JunD-mediated transcriptional activation of the miR-29b1 gene. JunD also enhanced formation of the Drosha microprocessor complex, thus further promoting miR-29b biogenesis. Cellular polyamines were found to regulate miR-29b expression by altering JunD abundance, since the increase in miR-29b expression levels in polyamine-deficient cells was abolished by JunD silencing. In addition, miR-29b silencing prevented JunD-induced repression of IEC proliferation. Our findings indicate that JunD activates miR-29b by enhancing its transcription and processing, which contribute to the inhibitory effect of JunD on IEC growth and maintenance of gut epithelium homeostasis.
authors: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland;
authors: Tongtong
authors: T
authors: Zou
authors: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland;
authors: Jaladanki N
authors: JN
authors: Rao
authors: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland;
authors: Lan
authors: L
authors: Liu
authors: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland;
authors: Lan
authors: L
authors: Xiao
authors: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland;
authors: Hee Kyoung
authors: HK
authors: Chung
authors: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland;
authors: Yanwu
authors: Y
authors: Li
authors: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland;
authors: Gang
authors: G
authors: Chen
authors: Laboratory of Genetics and Genomics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland; and.
authors: Myriam
authors: M
authors: Gorospe
authors: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland; Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland jwang@smail.umaryland.edu.
authors: Jian-Ying
authors: JY
authors: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D004848:Epithelium; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D014176:Protein Biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: C559371:JunD protein, human; C549531:JunD protein, rat; C526366:MIRN29 microRNA, rat; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D016755:Proto-Oncogene Proteins c-jun
keywords: cell proliferation; intestinal epithelial cells; microRNAs; transcriptional factors; transcriptional regulation