Authors

Weibing Tang, State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University; Laboratory of Modern Toxicology (Nanjing Medical University)
Junwei Tang, State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University; Laboratory of Modern Toxicology (Nanjing Medical University)
Jun He, Department of Pathology, Thomas Jefferson UniversityFollow
Zhigang Zhou, State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University; Laboratory of Modern Toxicology (Nanjing Medical University)
Yufeng Qin, State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University
Jingjing Qin, State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University; Laboratory of Modern Toxicology (Nanjing Medical University)
Bo Li, State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University; Laboratory of Modern Toxicology (Nanjing Medical University)
Xiaoqun Xu, State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University; Laboratory of Modern Toxicology (Nanjing Medical University)
Qiming Geng, Laboratory of Modern Toxicology (Nanjing Medical University)
Weiwei Jiang, Laboratory of Modern Toxicology (Nanjing Medical University)
Wei Wu, State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University
Xinru Wang, State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University
Yankai Xia, State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University

Document Type

Article

Publication Date

6-1-2015

Comments

This article has been peer reviewed. It was published in: Journal of Cellular and Molecular Medicine.

Volume 19, Issue 6, 1 June 2015, Pages 1197-1207.

The published version is available at DOI: 10.1111/jcmm.12454

Copyright © 2015 The Authors

Abstract

Hirschsprung's disease (HSCR) is a rare congenital disease caused by impaired proliferation and migration of neural crest cells. We investigated changes in expression of microRNAs (miRNAs) and the genes they regulate in tissues of patients with HSCR. Quantitative real-time PCR and immunoblot analyses were used to measure levels of miRNA, mRNAs, and proteins in colon tissues from 69 patients with HSCR and 49 individuals without HSCR (controls). Direct interactions between miRNAs and specific mRNAs were indentified in vitro, while the function role of miR-218-1 was investigated by using miR-218 transgenic mice. An increased level of miR-218-1 correlated with increased levels of SLIT2 and decreased levels of RET and PLAG1 mRNA and protein. The reductions in RET and PLAG1 by miR-218-1 reduced proliferation and migration of SH-SY5Y cells. Overexpression of the secreted form of SLIT2 inhibited cell migration via binding to its receptor ROBO1. Bowel tissues from miR-218-1 transgenic mice had nerve fibre hyperplasia and reduced numbers of gangliocytes, compared with wild-type mice. Altered miR-218-1 regulation of SLIT2, RET and PLAG1 might be involved in the pathogenesis of HSCR.

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