Cargando…

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

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 an...

Descripción completa

Detalles Bibliográficos
Autores principales: Tang, Weibing, Tang, Junwei, He, Jun, Zhou, Zhigang, Qin, Yufeng, Qin, Jingjing, Li, Bo, Xu, Xiaoqun, Geng, Qiming, Jiang, Weiwei, Wu, Wei, Wang, Xinru, Xia, Yankai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459835/
https://www.ncbi.nlm.nih.gov/pubmed/25786906
http://dx.doi.org/10.1111/jcmm.12454
_version_ 1782375277705297920
author Tang, Weibing
Tang, Junwei
He, Jun
Zhou, Zhigang
Qin, Yufeng
Qin, Jingjing
Li, Bo
Xu, Xiaoqun
Geng, Qiming
Jiang, Weiwei
Wu, Wei
Wang, Xinru
Xia, Yankai
author_facet Tang, Weibing
Tang, Junwei
He, Jun
Zhou, Zhigang
Qin, Yufeng
Qin, Jingjing
Li, Bo
Xu, Xiaoqun
Geng, Qiming
Jiang, Weiwei
Wu, Wei
Wang, Xinru
Xia, Yankai
author_sort Tang, Weibing
collection PubMed
description 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 PLAG1mRNA 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.
format Online
Article
Text
id pubmed-4459835
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BlackWell Publishing Ltd
record_format MEDLINE/PubMed
spelling pubmed-44598352015-06-16 SLIT2/ROBO1-miR-218-1-RET/PLAG1: a new disease pathway involved in Hirschsprung's disease Tang, Weibing Tang, Junwei He, Jun Zhou, Zhigang Qin, Yufeng Qin, Jingjing Li, Bo Xu, Xiaoqun Geng, Qiming Jiang, Weiwei Wu, Wei Wang, Xinru Xia, Yankai J Cell Mol Med Original Articles 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 PLAG1mRNA 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. BlackWell Publishing Ltd 2015-06 2015-03-19 /pmc/articles/PMC4459835/ /pubmed/25786906 http://dx.doi.org/10.1111/jcmm.12454 Text en © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Tang, Weibing
Tang, Junwei
He, Jun
Zhou, Zhigang
Qin, Yufeng
Qin, Jingjing
Li, Bo
Xu, Xiaoqun
Geng, Qiming
Jiang, Weiwei
Wu, Wei
Wang, Xinru
Xia, Yankai
SLIT2/ROBO1-miR-218-1-RET/PLAG1: a new disease pathway involved in Hirschsprung's disease
title SLIT2/ROBO1-miR-218-1-RET/PLAG1: a new disease pathway involved in Hirschsprung's disease
title_full SLIT2/ROBO1-miR-218-1-RET/PLAG1: a new disease pathway involved in Hirschsprung's disease
title_fullStr SLIT2/ROBO1-miR-218-1-RET/PLAG1: a new disease pathway involved in Hirschsprung's disease
title_full_unstemmed SLIT2/ROBO1-miR-218-1-RET/PLAG1: a new disease pathway involved in Hirschsprung's disease
title_short SLIT2/ROBO1-miR-218-1-RET/PLAG1: a new disease pathway involved in Hirschsprung's disease
title_sort slit2/robo1-mir-218-1-ret/plag1: a new disease pathway involved in hirschsprung's disease
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459835/
https://www.ncbi.nlm.nih.gov/pubmed/25786906
http://dx.doi.org/10.1111/jcmm.12454
work_keys_str_mv AT tangweibing slit2robo1mir2181retplag1anewdiseasepathwayinvolvedinhirschsprungsdisease
AT tangjunwei slit2robo1mir2181retplag1anewdiseasepathwayinvolvedinhirschsprungsdisease
AT hejun slit2robo1mir2181retplag1anewdiseasepathwayinvolvedinhirschsprungsdisease
AT zhouzhigang slit2robo1mir2181retplag1anewdiseasepathwayinvolvedinhirschsprungsdisease
AT qinyufeng slit2robo1mir2181retplag1anewdiseasepathwayinvolvedinhirschsprungsdisease
AT qinjingjing slit2robo1mir2181retplag1anewdiseasepathwayinvolvedinhirschsprungsdisease
AT libo slit2robo1mir2181retplag1anewdiseasepathwayinvolvedinhirschsprungsdisease
AT xuxiaoqun slit2robo1mir2181retplag1anewdiseasepathwayinvolvedinhirschsprungsdisease
AT gengqiming slit2robo1mir2181retplag1anewdiseasepathwayinvolvedinhirschsprungsdisease
AT jiangweiwei slit2robo1mir2181retplag1anewdiseasepathwayinvolvedinhirschsprungsdisease
AT wuwei slit2robo1mir2181retplag1anewdiseasepathwayinvolvedinhirschsprungsdisease
AT wangxinru slit2robo1mir2181retplag1anewdiseasepathwayinvolvedinhirschsprungsdisease
AT xiayankai slit2robo1mir2181retplag1anewdiseasepathwayinvolvedinhirschsprungsdisease