Abstract
Emerging evidence has demonstrated that long non-coding RNA Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) is associated with cellular behaviors among malignant tumors. However, the role of OIP5-AS1 in atherosclerosis remains largely undefined. The aim of this study was to explore the expression and role of OIP5-AS1 in a cell model of atherosclerosis, as well as the underlying mechanism. We found that expression of OIP5-AS1 was upregulated in human vascular smooth muscle cells (hVMSCs) under oxidized low density lipoprotein (ox-LDL) administration, and knockdown of OIP5-AS1 suppressed cell viability (CCK-8) and proliferating cell nuclear antigen (PCNA) protein level in ox-LDL-treated hVMSCs, as well as inhibited cell migration rate (wound healing assay) and protein expression of matrix metalloproteinase (MMP)-2 and MMP-9. Mechanically, OIP5-AS1 functioned as competing endogenous RNA (ceRNA) to positively regulate PAPPA expression through sponging miRNA-152-3p (miR-152), and pregnancy-associated plasma protein A (PAPPA) was identified as a downstream target gene for miR-152. Moreover, expression of miR-152 was downregulated and PAPPA was upregulated in ox-LDL-treated hVMSCs. Similarly to OIP5-AS1 knockdown, miR-215 overexpression could inhibit cell proliferation and migration of hVMSCs administrated by ox-LDL, which was abated by PAPPA upregulation. Moreover, miR-215 downregulation partially reversed the suppressive role of OIP5-AS1 knockdown as well. In conclusion, knockdown of OIP5-AS1 suppressed ox-LDL-treated hVMSC proliferation and migration presumably through targeting miR-152/PAPPA axis, suggesting a novel OIP5-AS1/miR-152/PAPPA pathway in atherogenesis.