Research Paper Volume 9, Issue 12 pp 2471—2479
MicroRNA-939 inhibits cell proliferation via targeting LRSAM1 in Hirschsprung’s disease
- 1 State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China
- 2 Key Laboratory of Modern Toxicology (Nanjing Medical University), Nanjing, China
- 3 Department of Pediatric Surgery, Children’s Hospital of Nanjing Medical University, Nanjing 210008, China
- 4 Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
received: July 10, 2017 ; accepted: November 26, 2017 ; published: December 18, 2017 ;https://doi.org/10.18632/aging.101331
How to Cite
Copyright: Chen et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Hirschsprung'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.
We 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.
Mir-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.
Our study shows the potential function of mir-939 through regulating LRSAM1 in HSCR and infers that autophagy may also confer the risk of HSCR.
HSCR: Hirschsprung's disease; miRNA: microRNA; LRSAM1: Leucine-rich repeat and sterile alpha motif-containing protein 1; ENCCs: Enteric neural crest cells; WB: Western blot; IHC: Immunohistochemical staining.