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

Background: 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.

Methods: 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.

Results: 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.

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