title: Nidogen-1 is a common target of microRNAs MiR-192/215 in the pathogenesis of Hirschsprung's disease.
abstract: Recent studies have emphasized the important role of microRNA (miRNA) clusters and common target genes in disease progression. Despite the known involvement of the miR-192/215 family in many human diseases, its biological role in Hirschsprung disease (HSCR) remains undefined. In this study, we explored the role of the miR-192/215 family in the pathogenesis of HSCR. Quantitative real-time PCR and western blotting measured relative expression levels of miRNAs, mRNAs, and proteins in 80 HSCR patients and 77 normal colon tissues. Targets were evaluated by dual-luciferase reporter assays, and the functional effects of miR-192/215 on human 293T and SH-SY5Y cells were detected by the Transwell assay, CCK8 assay and flow cytometry. MiR-192/215 was significantly down-regulated in HSCR tissue samples, and their knockdown inhibited cell migration and proliferation in the human 293T and SH-SY5Y cell lines. Nidogen 1 (NID1) was confirmed as a common target gene of miR-192/215 by dual-luciferase reporter gene assay and its expression was inversely correlated with that of miR-192/215 in tissue samples and cell lines. Silencing of NID1 could rescue the extent of the suppressing effects by miR-192/215 inhibitor. The down-regulation of miR-192/215 may contribute to HSCR development by targeting NID1. We proposed the following cascade for the proposed mechanism of miR-192/215 in the pathogenesis of Hirschsprung disease (HSCR) by targeting Nidogen 1 (NID1). Aberrant expression of miR-192/215 inhibits cell migration and cell proliferation via NID1. We think the miR-192/miR-215/NID1 signaling pathway may play an important role in the pathogenesis of HSCR.
authors: Department of Pediatric Surgery, Nanjing Children Hospital Affiliated Nanjing Medical University, Nanjing, China.|State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Dongmei
authors: D
authors: Zhu
authors: Department of Pediatric Surgery, Nanjing Children Hospital Affiliated Nanjing Medical University, Nanjing, China.|State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Hua
authors: H
authors: Xie
authors: Department of Pediatric Surgery, Nanjing Children Hospital Affiliated Nanjing Medical University, Nanjing, China.|State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Hongxing
authors: H
authors: Li
authors: Department of Pediatric Surgery, Nanjing Children Hospital Affiliated Nanjing Medical University, Nanjing, China.|State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Peng
authors: P
authors: Cai
authors: Department of Pediatric Surgery, Nanjing Children Hospital Affiliated Nanjing Medical University, Nanjing, China.|State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Hairong
authors: H
authors: Zhu
authors: Department of Pediatric Surgery, Nanjing Children Hospital Affiliated Nanjing Medical University, Nanjing, China.|State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Chao
authors: C
authors: Xu
authors: Department of Pediatric Surgery, Nanjing Children Hospital Affiliated Nanjing Medical University, Nanjing, China.|State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Pingfa
authors: P
authors: Chen
authors: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology (Nanjing Medical University), Ministry of Education, China.
authors: Ankur
authors: A
authors: Sharan
authors: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology (Nanjing Medical University), Ministry of Education, China.
authors: Yankai
authors: Y
authors: Xia
authors: Department of Pediatric Surgery, Nanjing Children Hospital Affiliated Nanjing Medical University, Nanjing, China.|State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Weibing
authors: W
authors: Tang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005260:Female; D057809:HEK293 Cells; D006627:Hirschsprung Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology
chemical_list: C546783:MIRN192 microRNA, human; C553667:MIRN215 microRNA, human; D008562:Membrane Glycoproteins; D035683:MicroRNAs; C029967:nidogen
keywords: 3′-UTR; HSCR; gene regulation; microRNA; neural crest cell; neural development