JunD enhances miR-29b levels transcriptionally and posttranscriptionally to inhibit proliferation of intestinal epithelial cells

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 increa...

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Published inAmerican Journal of Physiology: Cell Physiology Vol. 308; no. 10; pp. C813 - C824
Main Authors Zou, Tongtong, Rao, Jaladanki N, Liu, Lan, Xiao, Lan, Chung, Hee Kyoung, Li, Yanwu, Chen, Gang, Gorospe, Myriam, Wang, Jian-Ying
Format Journal Article
LanguageEnglish
Published United States American Physiological Society 15.05.2015
SeriesCell Signaling: Proteins, Pathways and Mechanisms
Subjects
Animals
Binding sites
Call for Papers
Cell Line
Cell Proliferation
Cells
Epithelial Cells - cytology
Epithelial Cells - metabolism
Epithelium
Homeostasis
Humans
Intestines - metabolism
MicroRNAs - metabolism
Mutation
Protein Biosynthesis
Protein expression
Proto-Oncogene Proteins c-jun - metabolism
Rats
Transcription, Genetic - physiology
microRNAs
intestinal epithelial cells
cell proliferation
transcriptional factors
transcriptional regulation
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Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.00027.2015