Circ_0068655 Promotes Cardiomyocyte Apoptosis via miR-498/PAWR Axis

Qiaoying Chai1,2, Mingqi Zheng1, Le Wang1

  • 1Department of Cardiovasology, the First Hospital of Hebei Medical University, No. 89 Donggang Road, Yuhua District, Shijiazhuang, Hebei, 050031, China.

Insights

Circular RNA circ_0068655 promotes cardiomyocyte apoptosis after myocardial infarction by regulating the miR-498-PAWR axis. This finding offers potential diagnostic and therapeutic strategies for MI patients.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • RNA Biology

Background:

  • Myocardial infarction (MI) leads to cardiac remodeling, significantly influenced by cardiomyocyte apoptosis.
  • Circular RNAs (circRNAs) are increasingly recognized for their roles in biological functions, but circ_0068655's function in MI remains unclear.
  • Investigating novel molecular mechanisms in cardiac injury is crucial for developing effective treatments.

Purpose of the Study:

  • To elucidate the role of circ_0068655 in myocardial infarction (MI) and its impact on human induced pluripotent stem-derived cardiomyocytes (HCMs).
  • To explore the molecular mechanism by which circ_0068655 influences cardiomyocyte apoptosis and cardiac remodeling.
  • To assess the potential of circ_0068655 as a diagnostic or therapeutic target for MI.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) and Western blotting to assess expression levels of circ_0068655, miR-498, and PAWR in MI tissues and HCMs.
  • Cell viability, cell death ELISA, and Caspase-3 activity assays to evaluate apoptosis.
  • Trans-well assays for cell migration analysis.
  • Luciferase reporter assays, miRNA pulldown assays, and Western blotting to confirm molecular interactions.

Main Results:

  • circ_0068655 and PAWR expression were upregulated, while miR-498 was downregulated in MI heart tissues and hypoxia-treated HCMs.
  • Inhibition of circ_0068655 attenuated hypoxia-induced cardiomyocyte apoptosis and improved cell migration.
  • circ_0068655 acts as a molecular sponge for miR-498, inhibiting its activity and consequently increasing PAWR expression.

Conclusions:

  • circ_0068655 promotes cardiomyocyte apoptosis in vitro via the miR-498-PAWR axis.
  • circ_0068655 demonstrates potential as a diagnostic biomarker and therapeutic target for myocardial infarction.
Abstract

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