Circular RNA WDR77 target FGF-2 to regulate vascular smooth muscle cells proliferation and migration by sponging...

Area of Science:

• Molecular Biology
• Cardiovascular Research
• Epigenetics

Background:

• Circular RNAs (circRNAs) are increasingly recognized for their roles in cardiovascular diseases.
• The specific expression patterns and regulatory functions of circRNAs in vascular smooth muscle cells (VSMCs) under high glucose conditions remain largely unknown.
• Understanding these mechanisms is crucial for addressing diabetes-related vasculopathy.

Purpose of the Study:

• To investigate the circRNA expression profiles in VSMCs exposed to high glucose in vitro.
• To identify specific circRNAs involved in regulating VSMC proliferation and migration.
• To elucidate the molecular mechanism of a key identified circRNA, circWDR77, in VSMC function.

Main Methods:

• CircRNA microarray analysis was performed on high glucose-induced VSMCs.
• Bioinformatic analyses were used to identify differentially expressed circRNAs and predict their targets.
• In vitro cell assays, including proliferation and migration assays, were conducted.
• RNA immunoprecipitation (RIP) and luciferase reporter assays validated molecular interactions.

Main Results:

• A total of 983 differentially expressed circRNAs were identified, with 458 upregulated and 525 downregulated.
• CircWDR77 was identified as a significantly upregulated circRNA.
• Silencing circWDR77 inhibited VSMC proliferation and migration.
• CircWDR77 was found to target miR-124 and fibroblast growth factor 2 (FGF-2).
• The circWDR77-miR-124-FGF2 pathway was confirmed to regulate VSMC proliferation and migration.

Conclusions:

• This study provides the first comprehensive circRNA expression profile in high glucose-induced VSMCs.
• CircWDR77 plays a critical role in regulating VSMC proliferation and migration.
• The circWDR77-miR-124-FGF2 regulatory pathway offers a potential therapeutic target for diabetes mellitus-associated vasculopathy.