TY - JOUR T1 - Long non-coding RNA LINC00657 acting as miR-590-3p sponge to facilitate low concentration oxidized low-density lipoprotein-induced angiogenesis JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.117.110650 SP - mol.117.110650 AU - Mei-hua Bao AU - Guang-yi Li AU - Xiao-shan Huang AU - Liang Tang AU - Li-ping Dong AU - Jian-ming Li Y1 - 2018/01/01 UR - http://molpharm.aspetjournals.org/content/early/2018/02/07/mol.117.110650.abstract N2 - Angiogenesis in atherosclerotic plaque promotes plaque growth, causes plaque hemorrhage and violates plaque stability. LINC00657 is a long noncoding RNA highly conserved and abundantly expressed in vascular endothelial cells. The present study was designed to investigate the effects and mechanisms of LINC00675 on the low concentration of oxidized low-density lipoprotein (oxLDL) induced angiogenesis. Cell proliferation assay, transwell assay, wound healing assay, and tube formation assay were conducted to detect the effects of low concentration of oxLDL on angiogenesis; The results discovered that oxLDL promoted the cell proliferation, migration, and tube formation. OxLDL also up-regulated LINC00657 expression. Inhibition of LINC00657 by siRNA significantly suppressed the oxLDL-induced endothelial cell proliferation, migration, and tube formation. Bioinformatic assay indicated six binding sites in LINC00657 sequence to miR-590-3p. The up-regulation of LINC00657 was related to the down-regulation of miR-590-3p in oxLDL-treated endothelial cells; while down-regulation of LINC00657 resulted in up-regulation of miR-590-3p. The anti-angiogenesis effects of si-LINC00657 were partly abrogated by miR-590-3p inhibitor. Further dual-luciferase assay found miR-590-3p inhibited the expression of HIF-1a by binding to the position of 689-696 in HIF-1a 3'-UTR directly. MiR-590-3p also inhibited the oxLDL-induced up-regulation of HIF-1a, VEGF, MMP-2, and MMP-9. These results suggested that in oxLDL treated endothelial cells, LINC00657 acted as a miR-590-3p sponge to attenuate the suppression of miR-590-3p on HIF-1a, and to promote angiogenesis through VEGF, MMP-2, and MMP-9. The present study provided a new insight into the roles of LINC00657 and miR-590-3p on preventing oxLDL-induced angiogenesis and may provide a novel strategy for atherosclerosis treatment. ER -