Long non-coding RNA PCA3 inhibits lipid accumulation and atherosclerosis through the miR-140-5p/RFX7/ABCA1 axis.

Objective: The purpose of this study was to explore the role of long noncoding RNA (lncRNA) prostate cancer antigen 3 (PCA3) in atherosclerosis and the underlying mechanism.

Methods: The Gene Expression Omnibus (GEO) datasets were used to divide differentially expressed lncRNAs, microRNAs (miRNAs), and mRNAs. The expression of PCA3, miR-140-5p, RFX7 and ABCA1 were determined by qPCR or Western blot in ox-LDL-treated macrophages. Macrophage lipid accumulation s was evaluated using the Oil Red O staining and high-performance liquid chromatography. Target relationships among PCA3, miR-140-5p, RFX7, and ABCA1 promoter area were validated via dual-luciferase reporter gene assay or chromatin immunoprecipitation assay. The apoE mouse model in vivo was designed to evaluate the effect of PCA3 on the reverse cholesterol transport (RCT) and atherosclerosis.

Results: PCA3 was down-regulated in foam cells, whereas miR-140-5p was highly expressed. Overexpression of PCA3 promoted ABCA1-mediated cholesterol efflux and reduced lipid accumulation in macrophages. Besides, RFX7 bound to the ABCA1 promoter and increased ABCA1 expression. Targeted relationships and interactions on the expression between miR-140-5p and PCA3 or RFX7 were elucidated. PCA3 up-regulated ABCA1 expression by binding to miR-140-5p to up-regulate RFX7 and ABCA1 expression in macrophages. PCA3 promoted RCT and impeded the progression of atherosclerosis by sponging miR-140-5p in apoE mice. Meanwhile, miR-140-5p also inhibit ABCA1 expression via downregulation of RFX7 to impede RCT and aggravate atherosclerosis.

Conclusions: lncRNA PCA3 promotes ABCA1-mediated cholesterol efflux to inhibit atherosclerosis through sponging miR-140-5p and up-regulating RFX7.