Abstract
The long noncoding RNA (lncRNA) MEG3 is involved in various biological processes including cell migration and cell proliferation. In present study, it was found that MEG3 and the intronic miR-770-5p were decreased in samples from HSCR patients. Besides, knockdown of MEG3 and miR-770-5p suppressed cell migration and proliferation, while cell cycle and apoptosis were not affected in human 293T and SH-SY5Y cells. SRGAP1 mRNA and protein upregulation was inversely correlated with miR-770-5p expression in tissue samples and cell lines, which was confirmed to be a target gene of miR-770-5p by dual-luciferase reporter assay. Moreover, silencing of SRGAP1 rescued the inhibition of cell migration and proliferation induced by MEG3 siRNA and miR-770-5p inhibition. The present study elucidates a novel mechanism of the development of HSCR and shows that the MEG3/miR-770-5p/SRGAP1 pathway plays a vital role in the pathogenesis of HSCR.
Highlights
Hirschsprung‘s disease (HSCR), a congenital enteric disease, is characterized by the absence of ganglion cells from various regions of the distal bowel caused by defects in the migration of neural crest-derived progenitor cells during embryogenesis [1, 2]
MEG3, the host gene of miR-770-5p, positively correlates with miR-770-5p expression in HSCR patients miR-770-5p is located in the intron of the long noncoding RNA (lncRNA) MEG3
LncRNAs are involved in various biological processes, including cell migration, cell proliferation, cell cycle progression, cell www.impactjournals.com/oncotarget apoptosis, and cell differentiation
Summary
Hirschsprung‘s disease (HSCR), a congenital enteric disease, is characterized by the absence of ganglion cells from various regions of the distal bowel caused by defects in the migration of neural crest-derived progenitor cells during embryogenesis [1, 2]. The incidence of HSCR is approximately 1:5000 live births with a 4:1 male:female gender bias [3]. Many genes have been associated with the pathogenesis of HSCR, including RET, GDNF, NRG1, EDNRB, SOX10 and so on [5,6,7]. The role of non-coding RNAs including long non-coding RNAs (lncRNA) and short non-coding RNAs (microRNA) have been expound to be involved in the appearance of HSCR [8, 9]
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