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.
Keywords: 3′-UTR; HSCR; gene regulation; microRNA; neural crest cell; neural development.
© 2015 International Society for Neurochemistry.