Long non-coding RNA NPPA-AS1 acts as a potential novel biomarker and promotes atrial fibrillation progression via the miR-302e/TGFBR2 axis

Atrial fibrillation (AF) has complex etiologies. This study aimed to investigate the clinical significance of long non-coding RNA (lncRNA) NPPA-AS1 in AF and the pro-AF mechanism of the NPPA-AS1/miR-302e/transforming growth factor beta receptor 2 (TGFBR2) axis. This study included 120 patients with AF and 120 healthy controls. An in vitro AF model was established by stimulating rat primary cardiac fibroblasts (CFs) with angiotensin II (AngII). RT-qPCR, Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) were utilized to assess gene expression, cellular function, and protein concentration, respectively. Molecular target regulation relationships were validated using RNA immunoprecipitation (RIP) and dual luciferase assays. Target genes predicted by multiple databases were selected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to investigate the biological functions and related signaling pathways of the NPPA-AS1/miR-302e axis. NPPA-AS1 was highly expressed in AF patients, serving as an independent risk factor for AF onset while demonstrating excellent diagnostic efficacy for AF. Its expression may be closely associated with cardiac structural remodeling, myocardial injury, and inflammatory responses in AF patients. Mechanistically, NPPA-AS1 was found to act as a molecular sponge to negatively regulate miR-302e, which directly suppressed TGFBR2 expression, forming the NPPA-AS1/miR-302e/TGFBR2 regulatory axis. In vitro, this regulatory axis was associated with Ang II-induced cellular proliferation, apoptosis imbalance, expression of fibrotic molecules, and inflammatory factor secretion (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6]), suggesting a potential role in AF-related pathological processes. Specifically, interference with NPPA-AS1 reversed these pathological effects, while inhibition of miR-302e counteracted this reversal. Further interference with TGFBR2 could re-block the pathological process. In vitro findings suggest that NPPA-AS1 may amplify AngⅡ-induced atrial fibrosis and inflammation by releasing TGFBR2 inhibition through “sponge-like” adsorption of miR-302e, indicating a potential contributory role in AF pathogenesis.