MicroRNA-939 inhibits cell proliferation via targeting LRSAM1 in Hirschsprung's disease

Aging (Albany NY). 2017 Dec 18;9(12):2471-2479. doi: 10.18632/aging.101331.

Abstract

BackgroundHirschsprung's disease (HSCR) is a common digestive disease caused by impaired development of neural crest cells. Some studies have revealed the roles of microRNA (miRNA) in various diseases. But the function of miRNA in HSCR needs further investigation.MethodsWe adopted qRT-PCR and immunoblot analyses to explore the relative expression of miR-939 and LRSAM1 in 80 HSCR bowel tissues and 80 normal bowel tissues. CCK-8 assay, transwell assay and flow cytometry were used to evaluate the function of miR-939 by overexpression of miR-939 in 293T, SK-N-BE(2), SH-SY5Y cell lines. The direct connection between miR-939 and LRSAM1 was validated by dual-luciferase reporter assay. We also investigated the autophagy level via immunoblot analyses.ResultsMir-939 was significantly upregulated in HSCR tissues with decreased expression of LRSAM1. Overexpression of miR-939 suppressed cell proliferation without affecting cell apoptosis, cell cycle or cell migration. And LRSAM1 exerted similar function. Autophagy was impaired in HSCR tissues compared with control samples. Mir-939 did not inhibit the autophagy although it decreased the expression of LRSAM1.ConclusionsOur study shows the potential function of mir-939 through regulating LRSAM1 in HSCR and infers that autophagy may also confer the risk of HSCR.

Keywords: Hirschsprung's disease; autophagy; microRNA (miRNA); migration; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / physiology
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation / genetics*
  • Hirschsprung Disease / genetics
  • Hirschsprung Disease / metabolism
  • Hirschsprung Disease / pathology*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • MIRN939 microRNA, human
  • MicroRNAs
  • LRSAM1 protein, human
  • Ubiquitin-Protein Ligases