SLIT 2/ROBO 1‐miR‐218‐1‐RET/PLAG 1: a new disease pathway involved in H irschsprung's disease
Open accessAbstract
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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Quite a few genes associated with selective sweeps in AMH examined here (among them RET, ZEB2, and SLIT2) have been linked to Hirschsprung disease.
“Quite a few genes associated with selective sweeps in AMH examined here (among them, RET, ZEB2, and SLIT2) have been linked to the disease [81, 82].”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [82]
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Self-domestication in Homo sapiens: Insights from comparative genomics
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- Authors
- Tang, W., Tang, J., He, J., Zhou, Z., Qin, Y., Qin, J., Li, B., Xu, X., Geng, Q., Jiang, W., Wu, W., Wang, X., & Xia, Y.
- Affiliations
- State Key Laboratory of Reproductive Medicine (CN)
- Thomas Jefferson University (US)
- Nanjing Children's Hospital (CN)
- Nanjing Medical University (CN)
- Corresponding author
- Xia, Yankai
- ORCID
- Venue
- Journal of Cellular and Molecular Medicine
- Publisher
- Wiley
- Published
- 2015-03-19
- Volume
- 19
- Issue
- 6
- Pages
- 1197-1207
- ISSN
- 1582-1838 (ISSN-L)
- 1582-4934
- PMC
- PMC4459835
- OpenAlex
- W2047222236
- Cited by
- 43
- References
- 28
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 3 · 2018: 6 · 2017: 6 · 2016: 7 · 2015: 5
- FWCI
- 8.06
- Type
- journal article
- Language
- en
- Update notices
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Cellular and Molecular Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (NSFC 81370473)
- Nanjing Medical Science and Technique Development Foundation (NMSTDF 201108010)
- riority Academic Program Development of Jiangsu Higher Education Institutions
- Topics
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- Hirschsprung disease, Slit2, ROBO1, RET, PLAG1, microRNA regulation, neural crest migration, colon
- MeSH terms
- Roundabout Proteins, Slit Homolog 2 Protein, Animals, Cell Movement, Colon, DNA-Binding Proteins, Female, Hirschsprung Disease, Humans, Infant, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Protein Binding, Receptors, Immunologic, Blotting, Western, Signal Transduction, Gene Expression, Reverse Transcriptase Polymerase Chain Reaction, MicroRNAs, Intercellular Signaling Peptides and Proteins, Cell Line, Tumor, Cell Proliferation, Proto-Oncogene Proteins c-ret
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