SLIT2/ROBO1‐miR‐218‐1‐RET/PLAG1: a new disease pathway involved in Hirschsprung's disease

Journal of Cellular and Molecular Medicine

Weibing Tang³  Junwei Tang³  Jun He²  Zhigang Zhou³  Yufeng Qin³  Jingjing Qin³  Bo Li³  Xiaoqun Xu³  Qiming Geng¹  Weiwei Jiang¹  Wei Wu³  Xinru Wang³ 

[1] Laboratory of Modern Toxicology (Nanjing Medical University), Ministry of Education, China;Department of Pathology, Thomas Jefferson University, Philadelphia, PA, USA;State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China

关键词: intestine;    gene regulation;    neural development;    genetic disorder;   

DOI  :  10.1111/jcmm.12454

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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