Circular RNA hsa_circ_0000118 promotes atrial fibrosis by regulating the microRNA‑34a‑5p/Smad4 axis.

Abstract

The regulatory functions and underlying mechanisms of circular RNAs (circRNAs/circs) in atrial fibrillation (AF) are largely unknown. The present study aimed to assess the prognostic roles and potential biological functions of hsa_circ_0000118 in structural remodeling in AF. Gain‑ and loss‑of‑function cell models were established in mouse cardiac fibroblasts. Cell Counting Kit‑8 and Transwell assays were used to analyze the proliferation and migration of cardiac fibroblasts. To evaluate the underlying mechanisms, RNA immunoprecipitation and luciferase reporter assays were performed. hsa_circ_0000118 was demonstrated to be significantly upregulated in atrial tissues of patients with valvular heart disease with AF compared to those without AF. Elevated plasma levels of hsa_circ_0000118 were independently associated with poor prognosis in patients with AF. In vitro, hsa_circ_0000118 promoted collagen I and collagen III expression, and the migration of cardiac fibroblasts. Functional assays demonstrated that hsa_circ_0000118 acted as a competing endogenous RNA of microRNA (miR)‑34a‑5p to reduce the suppressive effect of miR‑34a‑5p on its target Smad4 in cardiac fibroblasts. In conclusion, hsa_circ_0000118 may serve as a non‑invasive prognostic biomarker for AF. The newly identified roles of hsa_circ_0000118 in AF provide a mechanistic understanding of structural remodeling in AF and pave the way towards novel therapies.