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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.