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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2015
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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 |
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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 |
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