LncRNA HSPA7 in human atherosclerotic plaques sponges miR-223 and promotes the proinflammatory vascular smooth muscle cell transition

Abstract

Although there are many genetic loci in noncoding regions associated with vascular disease, studies on long noncoding RNAs (lncRNAs) discovered from human plaques that affect atherosclerosis have been highly limited. We aimed to identify and functionally validate a lncRNA using human atherosclerotic plaques. Human aortic samples were obtained from patients who underwent aortic surgery, and tissues were classified according to atherosclerotic plaques. RNA was extracted and analyzed for differentially expressed lncRNAs in plaques. Human aortic smooth muscle cells (HASMCs) were stimulated with oxidized low-density lipoprotein (oxLDL) to evaluate the effect of the identified lncRNA on the inflammatory transition of the cells. Among 380 RNAs differentially expressed between the plaque and control tissues, lncRNA HSPA7 was selected and confirmed to show upregulated expression upon oxLDL treatment. HSPA7 knockdown inhibited the migration of HASMCs and the secretion and expression of IL-1β and IL-6; however, HSPA7 knockdown recovered the oxLDL-induced reduction in the expression of contractile markers. Although miR-223 inhibition promoted the activity of Nf-κB and the secretion of inflammatory proteins such as IL-1β and IL-6, HSPA7 knockdown diminished these effects. The effects of miR-223 inhibition and HSPA7 knockdown were also found in THP-1 cell-derived macrophages. The impact of HSPA7 on miR-223 was mediated in an AGO2-dependent manner. HSPA7 is differentially increased in human atheroma and promotes the inflammatory transition of vascular smooth muscle cells by sponging miR-223. For the first time, this study elucidated the molecular mechanism of action of HSPA7, a lncRNA of previously unknown function, in humans.

LncRNA RASSF8-AS1 knockdown displayed antiproliferative and proapoptotic effects through miR-188-3p/ATG7 pathway in ox-LDL-treated vascular smooth muscle cells

“…Direct binding of lncRNA and miRNA appears to alter the cellular function of downstream molecules, leading to abnormalities of vascular endothelial cells and SMCs (39)(40)(41)(42). miR-188-3p was predicted to be targeted by RASSF8-AS1 based on bioinformatic analysis.…”

Non-Coding RNAs in Regulating Plaque Progression and Remodeling of Extracellular Matrix in Atherosclerosis

“…Although lncRNAs lack functional initiation codon and termination codons [184], some lncRNAs have been shown to translate into micropeptides [185]. In a study conducted by Ann et al [186], it was shown that among the 380 RNAs that differed in expression between plaque and control tissues, lncRNA HSPA7 was increased by oxidized low-density lipoprotein (oxLDL). HSPA7 knockdown decreased human aortic smooth muscle cell migration as well as IL-1 and IL-6 secretion and expression.…”

Long Noncoding RNA LINC00467: Role in Various Human Cancers

“…( Yan et al, 2022 ) Besides MIR17HG also inhibits non-small cell lung cancer via functioning as a ceRNA of miR-142-3p. ( Wei et al, 2020 ) Through this regulatory mode, lncRNAs are widely involved in the course of various diseases, including thyroid cancer ( Guo et al, 2021 ), renal fibrosis ( Tang et al, 2021 ), atherosclerotic plaques ( Ann et al, 2021 ), among others.…”