Knockdown of lncRNA H19 inhibits abnormal differentiation of small intestinal epithelial cells in diabetic mice
- 4 August 2018
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 234 (1), 837-848
- https://doi.org/10.1002/jcp.26902
Abstract
Diabetes mellitus (DM) comprises a group of metabolic diseases characterized by insulin deficiency or resistance and hyperglycemia. We previously reported the presence of abnormal differentiation of small intestinal epithelial cells (IECs) in diabetic mice, but the exact mechanism of this phenomenon has not been thoroughly elucidated to date. In this study, we found that H19 was markedly upregulated in IECs of DM mice. H19 knockdown significantly inhibited abnormal differentiation of IECs in DM mice. Bioinformatics analysis identified miR‐141‐3p as a candidate for H19. Based on luciferase reporter assays, we found that miR‐141‐3p directly targeted H19. Luciferase reporter assays also showed that miR‐141‐3p could directly target β‐catenin. Furthermore, H19 might act as an endogenous “sponge” by competing for miR‐141‐3p binding to regulate miRNA targets in vitro and in vivo. In summary, our findings provide the first evidence supporting the role of H19 in IECs of DM mice, and miR‐141‐3p targets not only protein‐coding genes but also the lncRNA H19.Funding Information
- Natural Science Foundation of Shandong Province (ZR2017BH103)
This publication has 51 references indexed in Scilit:
- Mapping the Human miRNA Interactome by CLASH Reveals Frequent Noncanonical BindingCell, 2013
- A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNACell, 2011
- Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in miceCell Research, 2011
- A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?Cell, 2011
- MicroRNAs Control Intestinal Epithelial Differentiation, Architecture, and Barrier FunctionGastroenterology, 2010
- Argonaute HITS-CLIP decodes microRNA–mRNA interaction mapsNature, 2009
- The intestinal stem cellGenes & Development, 2008
- Prevention and treatment of type 2 diabetes: Current role of lifestyle, natural product, and pharmacological interventionsPharmacology & Therapeutics, 2008
- Silencing of microRNAs in vivo with ‘antagomirs’Nature, 2005
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001