Circular RNA CCDC66 targets DCX to regulate cell proliferation and migration by sponging miR-488-3p in Hirschsprung's...

Area of Science:

• Molecular Biology
• Genetics
• Developmental Biology

Background:

• Circular RNAs (circRNAs) are increasingly recognized for their roles in biological processes and disease pathogenesis.
• The involvement of circRNAs in Hirschsprung's disease (HSCR), a congenital disorder, remains largely unexplored.

Purpose of the Study:

• To investigate the role of circRNAs in Hirschsprung's disease.
• To identify specific circRNAs and their molecular mechanisms in HSCR development.

Main Methods:

• Quantitative real-time PCR to measure circRNA expression levels.
• In vitro assays to assess the impact of circRNA reduction on cell proliferation and migration.
• Bioinformatic analysis to predict circRNA-RNA interactions.
• Luciferase reporter assays and RNA immunoprecipitation to validate molecular interactions.

Main Results:

• Circular RNA CCDC66 (cir-CCDC66) was found to be significantly downregulated in HSCR tissues compared to normal controls.
• Reduced cir-CCDC66 expression in vitro was associated with inhibited cell proliferation and migration.
• DCX transcript was identified as a potential target of cir-CCDC66 acting as a competing endogenous RNA (ceRNA).
• cir-CCDC66 functions as a molecular sponge for miR-488-3p, thereby regulating DCX RNA expression.

Conclusions:

• This study provides the first evidence of cir-CCDC66 dysregulation in Hirschsprung's disease.
• cir-CCDC66 modulates DCX expression by sponging miR-488-3p, suggesting a novel regulatory pathway in HSCR pathogenesis.
• These findings highlight the potential of cir-CCDC66 as a therapeutic target for HSCR.