Knockdown of LncRNA CCAT1 Attenuates ox-LDL-Induced Inflammation in THP1-Derived Macrophages via the miR-296-3p/FOSL1 Axis.

Macrophage-driven inflammation, induced by dysfunctional lipid metabolism, is a pivotal process in the pathogenesis of atherosclerosis (AS). While long noncoding RNAs (LncRNAs) are established regulators, the specific mechanisms governing their roles remain largely uncharacterized. Here, we demonstrate that the LncRNA colon cancer-associated transcript 1 (CCAT1) is significantly upregulated in THP1-derived macrophages upon stimulation with oxidized low-density lipoprotein (ox-LDL). Silencing LncRNA CCAT1 markedly attenuated the ox-LDL-induced inflammatory response, establishing its proinflammatory function. Mechanistically, we identified miR-296-3p as a direct downstream target of LncRNA CCAT1, which acts as a molecular sponge. This interaction was validated by dual-luciferase and RNA pull-down assays. Furthermore, we show that miR-296-3p suppresses inflammation by directly targeting the mRNA of FOS-like antigen 1 (FOSL1). Crucially, overexpression of LncRNA CCAT1 increased FOSL1 levels, confirming this regulatory axis. Collectively, our findings delineate a novel pro-inflammatory pathway where LncRNA CCAT1 promotes macrophage inflammation by sponging miR-296-3p, thereby derepressing its target FOSL1. Therefore, targeting LncRNA CCAT1 represents a promising therapeutic strategy for treating atherosclerotic cardiovascular disease.