Abstract
Long noncoding RNAs (lncRNAs) are untranslated transcripts greater than 200 nucleotides in length. Despite not being translated, they play a role in the regulation of transcription, translation, and other cellular processes and have been identified as key regulator in the progression of atherosclerosis. This study focused on the lncRNA X-inactive specific transcript (XIST), which participates in the regulation of X chromosome inactivation. XIST is produced by the XIST gene and is located on human chromosome Xql3.2. We also focused on discovering the possible role and mechanism of lncRNA XIST in oxidized low-density lipoprotein- (ox-LDL-) stimulated vascular smooth muscle cells (VSMCs), which could further help evalute its possible a role in the progression of atherosclerosis. XIST was overexpressed in ox-LDL-stimulated VSMCs, while the expression of miR-539-5p was decreased. XIST knockdown hindered the proliferation and migration of ox-LDL-treated VSMCs. XIST inhibits the miR-539-5p expression through direct interaction. Besides, miR-539-5p inhibitors can partially reverse the effect of XIST depletion on the proliferation and migration of VSMCs induced by ox-LDL stimulation. Further mechanistic analysis showed that secreted phosphoprotein 1 (SPP1) is the target of miR-539-5p, and XIST acts as a competing endogenous RNA for miR-539-5p to enhance the expression of SPP1. In addition, miR-539-5p inhibitor exerts its proliferation and migration effects by activating the miR-539-5p/SPP1 axis in VSMCs stimulated by ox-LDL. In conclusion, our study findings show that XIST inhibition can inhibit the proliferation and migration of atherosclerosis vascular smooth muscle cells, which provides a new theoretical basis for atherosclerosis treatment.