Mybl2, downregulated during colon epithelial cell maturation, is suppressed by miR-365
Open Access
- 1 September 2011
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Gastrointestinal and Liver Physiology
- Vol. 301 (3), G508-G518
- https://doi.org/10.1152/ajpgi.00066.2011
Abstract
Altered profiles of gene expression reflect the reprogramming of intestinal epithelial cells during their maturation along the crypt-luminal axis. To focus on genes important in this process, and how they in turn are regulated, we identified 14 transcripts commonly downregulated in expression during lineage-specific maturation of the immortalized cell lines Caco-2 (absorptive), HT29Cl16E (goblet), and HT29Cl19A (secretory) induced by contact inhibition of growth or the short-chain fatty acid butyrate. One such gene, Mybl2 (Myb-related protein B), has been linked to the stem cell phenotype, and we report is also markedly suppressed in maturing cells along the crypt-luminal axis in vivo. Mybl2 is not significantly downregulated transcriptionally during colon cell maturation, but we identified a potential micro-RNA (miRNA)-binding sequence in the Mybl2 3′-untranslated region that mediates reporter gene suppression in differentiating colon cells. Accordingly, miRNAs predicted to bind this functional target are upregulated in differentiating colon epithelial cells in vitro and in vivo; expression of one of these, hsa-miR-365 (but not hsa-324–5p), suppresses Mybl2 protein expression in proliferating Caco-2 cells. These data demonstrate that miRNA silencing plays an important role in regulating gene expression in maturing colon epithelial cells, and that utilizing a target-centered approach, rather than profiling global miRNA expression, can identify physiologically relevant, functional miRNAs.Keywords
This publication has 83 references indexed in Scilit:
- MYBL2, a link between proliferation and differentiation in maturing colon epithelial cellsJournal of Cellular Physiology, 2010
- miR-328 Functions as an RNA Decoy to Modulate hnRNP E2 Regulation of mRNA Translation in Leukemic BlastsCell, 2010
- Stem cell pluripotency: A cellular trait that depends on transcription factors, chromatin state and a checkpoint deficient cell cycleJournal of Cellular Physiology, 2009
- Proteomic changes during intestinal cell maturation in vivoJournal of Proteomics, 2008
- The MicroRNA miR-124 Promotes Neuronal Differentiation by Triggering Brain-Specific Alternative Pre-mRNA SplicingMolecular Cell, 2007
- Transactivation of miR-34a by p53 Broadly Influences Gene Expression and Promotes ApoptosisMolecular Cell, 2007
- A PCR-based method for detection and quantification of small RNAsBiochemical and Biophysical Research Communications, 2006
- MicroRNA expression profiles classify human cancersNature, 2005
- A microRNA polycistron as a potential human oncogeneNature, 2005
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001