CircRNA Larp4b/miR-298-5p/Mef2c Regulates Cardiac Hypertrophy Induced by Angiotensin II

Qihai Xie1,2, Xiangdong Xu3, Danqun Xiong3

  • 1Department of Cardiology, the First Affiliated Hospital of Soochow University, Suzhou, China.

Insights

Circular RNA Larp4b (circ_Larp4b) exacerbates cardiac hypertrophy by regulating the microRNA-298-5p/myocyte enhancer factor 2 axis. Downregulating circ_Larp4b may offer a therapeutic strategy for heart failure.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Genetics

Background:

  • Cardiac hypertrophy (CH) is a key indicator of heart failure progression.
  • Circular RNAs (circRNAs) are implicated in various human diseases.
  • The specific role of circ_Larp4b in myocardial hypertrophy remains uninvestigated.

Purpose of the Study:

  • To investigate the function of circ_Larp4b in Angiotensin II-induced cardiac hypertrophy.
  • To elucidate the molecular mechanism involving circ_Larp4b, microRNA-298-5p, and myocyte enhancer factor 2 (Mef2c) in CH.

Main Methods:

  • Established a cell model of CH using Angiotensin II (Ang II) treatment in HL-1 cells.
  • Quantified gene expression of circ_Larp4b, miR-298-5p, and Mef2c using qRT-PCR.
  • Assessed protein levels of CH markers (ACTN2, β-MHC, ANP) and Mef2c via Western blot.
  • Validated molecular interactions using dual-luciferase reporter and RNA pull-down assays.

Main Results:

  • Circ_Larp4b and Mef2c expression were elevated in Ang II-treated HL-1 cells.
  • Downregulation of circ_Larp4b attenuated Ang II-induced CH.
  • Circ_Larp4b acts as a sponge for miR-298-5p, which in turn targets Mef2c.
  • Overexpression of Mef2c counteracted the effects of miR-298-5p on cell size in the CH model.

Conclusions:

  • Circ_Larp4b promotes cardiac hypertrophy by modulating the miR-298-5p/Mef2c pathway.
  • Circ_Larp4b represents a potential therapeutic target for managing cardiac hypertrophy and heart failure.

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