Circ_0001490/miR-330-3p/RCAN1 Signaling Defines a ceRNA Network Associated with Rheumatic Heart Disease Progression

Circular RNAs (circRNAs) have been implicated in several cardiovascular disorders, yet their regulatory roles in rheumatic heart disease (RHD) and related molecular pathways remain poorly defined.

Human heart valve interstitial cells (hVICs) were manipulated by siRNA-mediated knockdown or plasmid-driven overexpression. Levels of circ_0001490, miR-330-3p, and regulator of calcineurin 1 (RCAN1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Cell Counting Kit-8 (CCK-8) was used to examine proliferation, whereas flow cytometry and Transwell assays were applied to evaluate apoptosis, migration, and invasion. Direct interactions among circ_0001490, miR-330-3p, and RCAN1 were tested by dual-luciferase reporter analysis and RNA immunoprecipitation.

Suppression of circ_0001490 reduced hVIC proliferation, migration, and invasion and increased apoptosis. miR-330-3p was verified as a direct circ_0001490 target; inhibition of miR-330-3p counteracted the phenotypic effects of circ_0001490 depletion. RCAN1 was further validated as a downstream target of miR-330-3p. Ectopic miR-330-3p expression restrained proliferation, migration, and invasion while enhancing apoptosis by downregulating RCAN1. Mechanistically, circ_0001490 increased RCAN1 expression by functioning as a miR-330-3p sponge.

The findings indicate that circ_0001490 may contribute to RHD progression by relieving miR-330-3p-mediated repression of RCAN1. Interference with circ_0001490, therefore, warrants further investigation as a potential strategy to limit RHD-associated cellular dysfunction.