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Circular RNA MGAT1 regulates cell proliferation and apoptosis in hypoxia-induced cardiomyocytes through miR-34a/YAP1

Pengyuan Chen1, Chaoran Zhou1, Bo Li2

  • 1Department of Pediatrics, Sichuan Academy of Medical Science/Sichuan Provincial People's Hospital Chengdu, Sichuan, China.

International Journal of Clinical and Experimental Pathology
|November 9, 2020
PubMed

Insights

Circular RNA MGAT1 (circMGAT1) protects against congenital heart disease (CHD) by inhibiting cell apoptosis and promoting cell proliferation via the miR-34a/YAP1 pathway. This finding offers a potential therapeutic target for CHD treatment.

Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • Genetics

Background:

  • Congenital heart disease (CHD) poses a significant global health burden with high morbidity and mortality.
  • Circular RNAs (circRNAs) are implicated in CHD pathogenesis, but their precise regulatory roles remain unclear.
  • Understanding the molecular mechanisms underlying CHD is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To elucidate the regulatory mechanism of circular RNA MGAT1 (circMGAT1) in the pathogenesis of human CHD.
  • To investigate the interaction between circMGAT1, miR-34a, and YAP1 in hypoxia-induced cardiomyocytes.

Main Methods:

  • Quantitative polymerase chain reaction (qRT-PCR) to measure circMGAT1 and miR-34a expression.
  • Western blot to assess YAP1 expression.
  • Cell proliferation (CCK-8 assay), apoptosis (flow cytometry), dual-luciferase reporter, and RNA immunoprecipitation (RIP) assays were performed.

Main Results:

  • circMGAT1 levels were downregulated, while miR-34a was upregulated in CHD tissues and hypoxia-induced AC16 cells.
  • circMGAT1 acted as a sponge for miR-34a, regulating cardiomyocyte proliferation and apoptosis.
  • miR-34a directly targeted YAP1, and circMGAT1 modulated YAP1 expression by sponging miR-34a.

Conclusions:

  • circMGAT1 inhibits apoptosis and enhances proliferation in hypoxia-induced cardiomyocytes by regulating the miR-34a/YAP1 axis.
  • The circMGAT1/miR-34a/YAP1 pathway represents a potential therapeutic target for treating human CHD.
  • This study provides novel insights into the molecular underpinnings of CHD, paving the way for targeted interventions.

Keywords:
CHDYAP1apoptosiscircMGAT1miR-34aproliferation

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