Circ_0001052 promotes cardiac hypertrophy via elevating Hipk3

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.