CASC15 participated in the damage of vascular endothelial cells in atherosclerosis through interaction with miR-940

This study aimed to explore the role of long non-coding RNA cancer Susceptibility 15 (CASC15) and microRNA (miR)-940 in atherosclerosis (AS) and to elucidate their potential mechanisms of action using an in vitro cell model of AS.

Human umbilical vein endothelial cells (HUVECs) were subjected to oxidized low-density lipoproteins (ox-LDL) induction to establish an atherosclerotic cell model, and the expression levels of CASC15 and miR-940 in this model were evaluated. Cell viability and apoptosis were detected using the Cell Count Kit (CCK)-8 assay and flow cytometry, respectively. Quantitative real-time PCR was employed to quantify gene expression levels of CASC15, miR-940, and cell adhesion molecules intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, while Enzyme-linked immunosorbent assay was used to measure the protein levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Bioinformatics analysis was utilized to explore the target genes of miR-940 and their functional implications.

The expression of CASC15 and miR-940 in ox-LDL-induced HUVECs showed an increase in CASC15 and a decrease in miR-940. Notably, miR-940 is a downstream target gene of CASC15. CASC15 knockdown mitigated ox-LDL-induced autophagy flux impairment, thereby promoting autophagy, whereas decreased levels of miR-940 significantly inhibit autophagy. Inhibition of CASC15 alleviates endothelial dysfunction caused by ox-LDL primarily through promoting activity and reducing apoptosis and inflammation. Conversely, a decrease in miR-940 exacerbates endothelial dysfunction. The addition of an autophagy activator relieved endothelial dysfunction, highlighting the involvement of the CASC15/miR-940 axis in regulating autophagy, and its role in modulating endothelial function impairment through autophagy regulation.

Inhibition of CASC15 alleviates ox-LDL-induced endothelial dysfunction, potentially through the activation of autophagy via the modulation of miR-940.