lncRNA RP11‑531A24.3 inhibits the migration and proliferation of vascular smooth muscle cells by downregulating ANXA2 expression

Abstract

A complete understanding of the behavioral influence and phenotypic transition of vascular smooth muscle cells, as well as the effects of the characteristics of these cells on the physiological and pathological processes of atherosclerosis, is crucial if new therapeutic targets for atherosclerosis are to be identified. In the present study, the long non-coding RNA RP11-531A24.3 was identified to be expressed at low levels in plaque tissues through screening a microarray for differentially expressed genes. The functional experimental results suggested that RP11-531A24.3 reduced the viability and inhibited the migration of human aortic vascular smooth muscle cells (HA-VSMCs). RNA antisense purification-mass spectrometry was used to identify the RNA-binding proteins (RBPs) for RP11-531A24.3. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the pathway with the highest degree of association with RP11-531A24.3 RBPs was related to cell migration. The reduced migration and viability mediated by RP11-531A24.3 overexpression was more significantly suppressed after annexin 2 (ANXA2) depletion in RP11-531A24.3-overexpressing HA-VSMCs. Culture of HA-VSMCs under hypoxic conditions (1% O 2 ) reduced the expression of RP11-531A24.3, and enhanced the protein expression of ANXA2 and HIF-1α, while knockdown of ANXA2 downregulated the protein expression of HIF-1α.These results suggested that RP11-531A24.3 regulated the proliferation and migration of HA-VSMCs through ANXA2 expression, and hypoxia may be an external factor in the regulation of RP11-531A24.3 and its downstream targets.

Long non-coding RNAs: Modulators of phenotypic transformation in vascular smooth muscle cells

“…LncRNA BANCR overexpression induces HASMC proliferation by downregulating miR-34c methylation and reversing the effect of miR-34c on HMGB1, TNF-α, and Bcl-2 expression, thereby promoting HASMCs proliferation and inhibiting apoptosis (30). The expression of LncRNA RP11-531A24.3 is reduced in advanced AS lesions; in cells overexpressing it, lncRNA RP11-531A24.3 inhibits the migration and proliferation of HA-VSMCs by binding directly to the RNA-binding protein annexin 2 (ANXA2) in the cytoplasm to reduce its expression at the mRNA and protein levels (31).…”

LncRNAs Involved in the Regulation of Vascular Smooth Muscle Cell Proliferation and Migration in Atherosclerosis

“…LncRNA RP11-531A24.3 is down-regulated in atherosclerotic plaque tissues. Yilin Wu et al [31]found that LncRNA rp11-531a24.3 plays a role in inhibiting theproliferation and migration of VSMCs by inhibiting the expression of ANXA2 mRNA and protein levels.ANXA2, a member of the calcium-dependent phospholipid-binding protein family, enhances proliferation and migration in various cancers and is associated with smooth muscle contraction [32].…”