STARD4-AS1 promotes coronary artery disease and modulates endothelial dysfunction by targeting miR-204-3p/FLI1.

[BACKGROUND] Coronary artery disease (CAD) remains the primary cause of mortality and disability-adjusted life years lost worldwide. This study focuses on elucidating the expression, cell functions, and possible regulatory mechanisms of the steroidogenic acute regulator protein-related lipid transfer domain containing 4-antisense RNA 1 (STARD4-AS1) in CAD.

[METHODS] GSE113079 dataset was used to identify the studied lncRNA. Serum STARD4-AS1 levels were quantified by RT-qPCR in a cohort of 88 CAD patients and 72 healthy participants. In vitro functional assays were performed in human primary coronary artery endothelial cells (HCAECs) under hypoxia following transfection with STARD4-AS1 siRNA. The cell function assays encompassed monocyte adhesion, lactate dehydrogenase (LDH) release, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and low-density lipoprotein cholesterol (LDL-C). A downstream miRNA for STARD4-AS1 was predicted and validated via dual-luciferase reporter assays. Rescue experiments were conducted for the function assays of STARD4-AS1/miRNA axis.

[RESULTS] GSE113079 dataset revealed a significant elevation of STARD4-AS1 in CAD peripheral blood mononuclear cells. In CAD serum, STARD4-AS1 level was elevated. The STARD4-AS1 upregulation was positively correlated with LDL-C levels and had a diagnostic value for CAD. Under hypoxia, the knockdown of STARD4-AS1 mitigated the LDH release, MDA levels, the intracellular LDL-C content, and monocyte adhesion to HCAECs. MiR-204-3p was identified as a target miRNA for STARD4-AS1, while Friend leukemia virus integration 1 (FLI1) was a target gene for miR-204-3p. MiR-204-3p inhibition can offset the functions of STARD4-AS1 suppression on HCAECs exposed to hypoxic conditions.

[CONCLUSION] STARD4-AS1 can regulate endothelial cell functions under hypoxic conditions. This study highlights its potential as a novel therapeutic target and a promising circulating biomarker candidate for CAD.