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Circ_0001052 promotes cardiac hypertrophy via elevating Hipk3

Mengyue Yang1, Weichen Wang1, Longlong Wang1

  • 1Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China.

Aging
|February 17, 2023
PubMed

Insights

Circular RNA circ_0001052 promotes cardiac hypertrophy by increasing homeodomain-interacting protein kinase 3 (Hipk3) levels. This occurs by sponging microRNAs and recruiting Srsf1, highlighting a novel mechanism in cardiac disease.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Epigenetics

Background:

  • Cardiac hypertrophy (CH) is a major risk factor for sudden cardiac death.
  • Circular RNAs (circRNAs) play critical roles in various biological and pathological processes.
  • Circ_0001052, derived from Hipk3, has been implicated in aggravating myocardial fibrosis.

Purpose of the Study:

  • To elucidate the role and underlying mechanism of circ-Hipk3 in cardiac hypertrophy.
  • To investigate the regulatory network involving circ_0001052, Hipk3, microRNAs, and Srsf1 in CH.

Main Methods:

  • Established *in vivo* (transverse aortic constriction) and *in vitro* (angiotensin II treatment of cardiomyocytes) models of cardiac hypertrophy.
  • Verified circular characteristics of circ_0001052 and assessed its regulatory effects on Hipk3.
  • Conducted rescue assays to evaluate the functional roles of circ_0001052, Hipk3, miR-148a-3p, miR-124-3p, and Srsf1.

Main Results:

  • Circ_0001052 demonstrated pro-hypertrophic effects in angiotensin II-treated cardiomyocytes.
  • Circ_0001052 positively regulated Hipk3 expression, with Hipk3 exhibiting similar functional effects.
  • Circ_0001052 acted as a competing endogenous RNA (ceRNA) for miR-148a-3p and miR-124-3p, and recruited Srsf1 to stabilize Hipk3.
  • miR-148a-3p and miR-124-3p partially reversed the pro-hypertrophic effects of circ_0001052.

Conclusions:

  • Circ_0001052 promotes cardiac hypertrophy by up-regulating Hipk3 expression.
  • The mechanism involves circ_0001052 sponging miR-148a-3p and miR-124-3p, and recruiting Srsf1 to stabilize Hipk3.
  • This study reveals a novel circRNA-mediated regulatory pathway contributing to cardiac hypertrophy progression.

Keywords:
Hipk3Srsf1cardiac hypertrophycircRNA

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