IGF2-derived miR-483-3p associated with Hirschsprung's disease by targeting FHL1

Abstract

HSCR (Hirschsprung's disease) is a serious congenital defect, and the aetiology of it remains unclear. Many studies have highlighted the significant roles of intronic miRNAs and their host genes in various disease, few was mentioned in HSCR although. In this study, miR-483-3p along with its host gene IGF2 (Insulin-like growth factor 2) was found down-regulated in 60 HSCR aganglionic colon tissues compared with 60 normal controls. FHL1 (Four and a half LIM domains 1) was determined as a target gene of miR-483-3p via dual-luciferase reporter assay, and its expression was at a higher level in HSCR tissues. Here, we study cell migration and proliferation in human 293T and SH-SY5Y cell lines by performing Transwell and CCK8 assays. In conclusion, the knockdown of miR-483-3p and IGF2 both suppressed cell migration and proliferation, while the loss of FHL1 leads to opposite outcome. Furthermore, miR-483-3p mimics could rescue the negative effects on cell proliferation and migration caused by silencing IGF2, while the FHL1 siRNA may inverse the function of miR-483-3p inhibitor. This study revealed that miR-483-3p derived from IGF2 was associated with Hirschsprung's disease by targeting FHL1 and may provide a new pathway to understand the aetiology of HSCR.

Keywords: Hirschsprung's disease; four and a half LIM domains 1; gene regulation; insulin-like growth factor 2; miR-483-3p.