Loss of circIGF1R Suppresses Cardiomyocytes Proliferation by Sponging miR-362-5p

Jun-Hui Zeng1, Hong-Ji Li1, Kun Liu1

  • 1Key Laboratory of Regenerative Medicine of Ministry of Education, Department of Developmental & Regenerative Biology, Jinan University, Guangzhou, China.

DNA and Cell Biology
|June 22, 2023
PubMed

Insights

Circular RNAs (circRNAs) regulate cardiomyocyte proliferation. Circ-insulin-like growth factor 1 receptor (circIGF1R) promotes proliferation by sponging miR-362-5p, increasing PHF3 expression, crucial for heart regeneration.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Epigenetics

Background:

  • Circular RNAs (circRNAs) are increasingly recognized for their roles in cardiovascular diseases.
  • The specific function of circ-insulin-like growth factor 1 receptor (circIGF1R) in cardiomyocyte proliferation is not well understood.

Purpose of the Study:

  • To investigate the role of circIGF1R in cardiomyocyte proliferation.
  • To elucidate the molecular mechanism by which circIGF1R influences cardiomyocyte growth.

Main Methods:

  • Expression analysis of circIGF1R, miR-362-5p, and PHF3 in neonatal and adult mouse hearts, and in injured hearts.
  • Functional assays involving circIGF1R knockdown and miR-362-5p mimics/inhibition in primary cardiomyocytes.
  • Luciferase reporter assays to confirm the interaction between circIGF1R and miR-362-5p.
  • Quantitative real-time PCR (qPCR) for gene expression validation.

Main Results:

  • circIGF1R expression was lower in adult hearts and increased in injured neonatal hearts.
  • circIGF1R knockdown inhibited cardiomyocyte proliferation, while its overexpression promoted it.
  • circIGF1R directly interacted with miR-362-5p, acting as a sponge.
  • miR-362-5p suppressed cardiomyocyte proliferation and targeted PHF3.
  • PHF3 expression was decreased in adult hearts and increased in injured neonatal hearts.
  • Knockdown of PHF3 inhibited cardiomyocyte proliferation.

Conclusions:

  • circIGF1R promotes cardiomyocyte proliferation by sponging miR-362-5p, leading to increased PHF3 expression.
  • This circIGF1R/miR-362-5p/PHF3 axis is a novel regulatory pathway for cardiomyocyte proliferation and heart regeneration.

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