Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 34, Issue 2, Pages 543-553Publisher
KARGER
DOI: 10.1159/000363021
Keywords
HSCR; 3 '-UTR; Neural crest cell; Neural development; Pediatric
Categories
Funding
- Natural Science Foundation of China [NSFC 81370473]
- Natural Science Foundation of Jiangsu Province of China [BK20131388]
- Scientific Research Project of Jiangsu Provincial Department of health [H201342]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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Background/Aims: Hirschsprung's disease (HSCR) is a genetic disorder of neural crest development. In this study, we investigated whether and how miR-200a and miR-141, belonging to miR-200 family, were involved in the pathogenesis of HSCR. Methods: Quantitative real time PCR and Western blot were used to detect the levels of miRNA, mRNAs, and proteins in colon tissues from 88 HSCR patients and 75 controls. The direct regulation of specific mRNA by miRNAs was validated by dual-luciferase reporter assay and RNA interference in cell lines. Transwell assays, CCK8 assay, and flow cytometry were inplemented to measure viability and activities of human 293T and SH-SY5Y cells, respectively. Results: Aberrant suppression of miR-200a was observed in colon tissues of HSCR patients. A decreased level of miR-200a and miR-141 correlated with increased levels of PTEN mRNA and protein. The Dual-Luciferase reporter gene assay demonstrated that miR-200a and miR-141 binded directly to 3'UTR of PTEN and resulting in the inhibition of PTEN. The reductions in miR-200a and miR-141 inhibited migration and proliferation of 293T and SH-SY5Y cells through up-regulating the expression of PTEN. Moreover, knocking-down of PTEN rescued the extent of suppressed cell migration and proliferation induced by miR-200a and miR-141. Conclusions: The miR-200 family may play a crucial role in the pathogenesis of HSCR by co-regulating PTEN. Copyright (C) 2014 S. Karger AG, Basel
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