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Downregulation of microRNA-483-5p Promotes Cell Proliferation and Invasion by Targeting GFRA4 in Hirschsprung's

Gang Wang1, Feng Guo1, Hefeng Wang1

  • 1Department of Pediatric Surgery, Shandong Province Hospital Affiliated to Shandong University , Jinan, China .

DNA and Cell Biology
|November 2, 2017
PubMed

Insights

MicroRNA-483-5p (miR-483-5p) is elevated in Hirschsprung

Area of Science:

  • Genetics
  • Molecular Biology
  • Developmental Biology

Background:

  • MicroRNAs (miRNAs) are crucial regulators of gene expression implicated in disease progression.
  • The specific role of microRNA-483-5p (miR-483-5p) in Hirschsprung's disease (HSCR) pathogenesis is currently undefined.
  • Understanding miRNA functions is vital for elucidating disease mechanisms.

Purpose of the Study:

  • To investigate the biological function and role of miR-483-5p in the pathogenesis of Hirschsprung's disease (HSCR).
  • To identify downstream targets of miR-483-5p relevant to HSCR.
  • To explore the therapeutic potential of targeting miR-483-5p in HSCR.

Main Methods:

  • Histological analysis of colonic tissues using hematoxylin and eosin (HE) staining.
  • Quantitative real-time PCR and western blotting to assess miRNA, mRNA, and protein expression levels.
  • Cellular assays (CCK-8, flow cytometry, Transwell) to evaluate cell proliferation, cycle, invasion, and apoptosis.
  • Dual-luciferase reporter gene assay to confirm direct targeting of GFRA4 by miR-483-5p.

Main Results:

  • miR-483-5p expression was significantly increased in HSCR tissues compared to normal controls.
  • Downregulation of miR-483-5p inhibited cell proliferation, cell cycle progression, and invasion, while promoting apoptosis in HSCR cell lines.
  • GFRA4 was identified as a direct downstream target of miR-483-5p, exhibiting an inverse correlation in expression levels.

Conclusions:

  • miR-483-5p plays a significant role in the pathogenesis of Hirschsprung's disease.
  • The miR-483-5p/GFRA4 axis is a key regulatory pathway in HSCR.
  • Targeting miR-483-5p may offer a potential therapeutic strategy for HSCR.
Keywords:
GFRA4Hirschsprung's diseasecell proliferationmiR-483-5p

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