Aberrant expression of LINC00346 regulates cell migration and proliferation via competitively binding to miRNA-148a-3p/Dnmt1 in Hirschsprung’s disease
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In brief
In brief
Study identifies LINC00346 as a downregulated long noncoding RNA in Hirschsprung's disease that regulates enteric neural crest cell development through a competing endogenous RNA mechanism. LINC00346 acts as a molecular sponge for miR-148a-3p, modulating Dnmt1 expression and affecting cell proliferation, migration, and apoptosis in disease pathogenesis.
Written by the GCMD Library team from the article.
Abstract
Background
Hirschsprung’s disease (HSCR) is a common birth defect caused by dysplasia of neural crest cells in the gut. Long noncoding RNAs (lncRNAs) play an important role in cellular processes, including development and disease. Despite the known engagement of LINC00346 in several human diseases, its biological function in HSCR remains unknown.
Methods
The relative expression levels of LINC00346, miR-148a-3p and Dnmt1 in HSCR colon tissues were detected by quantitative real-time PCR. Western blot assays were conducted to investigate the Dnmt1 protein expression level. Knockdown of LINC00346 and overexpression of miR-148a-3p in SH-SY5Y and SK-N-BE(2) cell lines was conducted. Cell proliferation and migration were detected by cell counting Kit-8 assays, 5-ethynyl-2′-deoxyuridine assays and transwell assays. Cell apoptosis was verified by flow cytometric analysis. Furthermore, the competing endogenous RNA (ceRNA) activity of LINC00346 on miR-148a-5p was investigated via bioinformatics analysis and luciferase reporter assays.
Result
Downregulation of LINC00346 and Dnmt1 was detected in HSCR tissues. Knockdown of LINC00346 and overexpression of miR-148a-3p in SK-N-BE(2) and SH-SY5Y cells inhibited cell migration and proliferation and promoted apoptosis. Moreover, the miR-148a-3p inhibitor rescued the downregulation of Dnmt1 in LINC00346 knockdown cell lines, which was evidence of the ceRNA regulatory mechanism of Dnmt1 by LINC00346.
Conclusions
LINC00346 was downregulated in HSCR colon tissues and acted as a ceRNA to regulate the expression of Dnmt1 in vitro. Together, these findings indicate that LINC00346 could affect the occurrence of HSCR by participating in the development of enteric neural crest cells.