LINC01140 Alleviates the Oxidized Low-Density Lipoprotein-Induced Inflammatory Response in Macrophages via Suppressing miR-23b
Our previous study has demonstrated that miR-23b enhances oxidized low-density lipoprotein (oxLDL)-induced inflammatory response of macrophages through the A20/NF-κB signaling pathway, thus contributing to atherosclerosis. This study aims to further investigate the upstream regulators of miR-23b in mediating oxLDL-induced inflammatory response. Human monocyte cell line THP1 was induced to differentiate into macrophages followed by the oxLDL stimulation of inflammatory response. The expression of miR-23b, LINC01140, and p53 mRNA was detected by quantitative PCR. The combination of miR-23b and LINC01140 was confirmed by luciferase reporter assay and RNA immunoprecipitation. The binding of p53 and LINC01140 promoter was determined by luciferase reporter assay. The level of inflammatory cytokines, including MCP-1, TNF-α, and IL-1β, was assessed by enzyme-linked immunosorbent assay. LINC01140 was downregulated, while p53 and miR-23b were upregulated in oxLDL-induced inflammatory response of macrophages. Overexpression of LINC01140 reduced NF-κB activity by reducing miR-23b and increasing A20. The transcription of LINC01140 was inhibited by binding of p53 and the LINC01140 promoter region. Knockdown of p53 significantly reduced NF-κB activity and level of inflammatory cytokines by promoting LINC01140 expression. Our findings demonstrated that LINC01140 acts as an anti-inflammatory factor through negatively regulating miR-23/A20 axis. In addition, p53 is identified as a transcriptional repressor of LINC01140.
KEY WORDSlong non-coding RNA p53 macrophage NF-κb activity A20
The study was supported by Scientific and Technological Project of Inner Mongolia Autonomous Region (No. 201602098).
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