LOXL1-AS1/miR-515-5p/STAT3 Positive Feedback Loop Facilitates Cell Proliferation and Migration in Atherosclerosis

Abstract: Existing research has elucidated the critical role of long noncoding RNAs (lncRNAs) in the progression of multiple human cardiovascular diseases, including atherosclerosis (AS). Nonetheless, whether long noncoding RNA LOXL1 antisense RNA 1 (LOXL1-AS1) regulates the biological functions in AS is exceedingly limited. In this research, we detected through reverse transcription-quantitative polymerase chain reaction that LOXL1-AS1 expression was markedly upregulated in patients with AS. The role of LOXL1-AS1 in vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) was unmasked by functional assays. Moreover, knockdown of LOXL1-AS1 exerted suppressive effect on proliferation and migration whereas accelerated apoptosis in VSMCs and HUVECs. Molecular mechanism assays revealed that signal transducer and activator of transcription 3 (STAT3) functioned as a transcription activator of LOXL1-AS1 in VSMCs and HUVECs. In addition, miR-515-5p was manifested to bind with LOXL1-AS1 (or STAT3) in VSMCs and HUVECs. Furthermore, LOXL1-AS1 could elevate STAT3 expression by sponging miR-515-5p in VSMCs and HUVECs. More importantly, rescue assays delineated that inhibited expression of miR-515-5p or elevated expression of STAT3 could reverse the restraining effect of LOXL1-AS1 depletion on the progression of AS in HUVECs. All these findings revealed the role of a LOXL1-AS1/miR-515-5p/STAT3 positive feedback loop in AS.