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Nidogen‐1 is a common target of micro RNA s MiR‐192/215 in the pathogenesis of Hirschsprung's disease
Author(s) -
Zhu Dongmei,
Xie Hua,
Li Hongxing,
Cai Peng,
Zhu Hairong,
Xu Chao,
Chen Pingfa,
Sharan Ankur,
Xia Yankai,
Tang Weibing
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13118
Subject(s) - microrna , pathogenesis , gene silencing , gene knockdown , hek 293 cells , biology , cell growth , flow cytometry , blot , reporter gene , cell culture , cell , cancer research , microbiology and biotechnology , gene expression , gene , immunology , genetics
Recent studies have emphasized the important role of micro RNA (mi RNA ) 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 mi RNA s, mRNA s, 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 ‐ SY 5Y cells were detected by the Transwell assay, CCK 8 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 ‐ SY 5Y cell lines. Nidogen 1 ( NID 1) 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 NID 1 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 NID 1.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.