LncRNA KCNQ1OT1 knockdown inhibits ox-LDL-induced inflammatory response and oxidative stress in THP-1 macrophages through the miR-137/TNFAIP1 axis.

Both inflammatory response and oxidative stress are regarded as two critical contributors to atherosclerosis. Kcnq1 overlapping transcript 1 (KCNQ1OT1) is an imprinted antisense long non-coding RNA in the kcnq1 locus. Our previous study has demonstrated that KCNQ1OT1 aggravates atherosclerosis by promoting macrophage lipid accumulation. However, its role in atherogenesis remains to be elucidated. This study aimed to observe the impact of KCNQ1OT1 on oxidized low-density lipoprotein (ox-LDL)-induced inflammatory response and oxidative stress and to explore the underlying mechanism. We found that ox-LDL up-regulated KCNQ1OT1 expression in THP-1 macrophages. Knockdown of KCNQ1OT1 increased miR-137 levels, decreased tumor necrosis factor-α-induced protein 1 (TNFAIP1) expression, and inhibited inflammatory response and alleviated oxidative stress in ox-LDL-treated THP-1 macrophages. A ceRNA regulatory network was identified among KCNQ1OT1, miR-137 and TNFAIP1. The inhibitory effect of KCNQ1OT1 knockdown on inflammatory response and oxidative stress was significantly reversed by miR-137 prevention or TNFAIP1 overexpression. In summary, these findings suggest that silencing of KCNQ1OT1 suppresses inflammatory response and oxidative stress induced by ox-LDL through the miR-137/TNFAIP1 pathway in THP-1 macrophages, thereby providing novel mechanistical insights into its pro-atherosclerotic action.