Blockade of NEAT1 represses inflammation response and lipid uptake via modulating miR‐342‐3p in human macrophages THP‐1 cells

• Published in: Journal of cellular physiology 2019-04, Vol.234 (4), p.5319-5326
• Main Authors: Wang, Lei, Xia, Jing‐Wen, Ke, Zun‐Ping, Zhang, Bing‐Hong
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; Arteriosclerosis; Atherosclerosis; Atherosclerosis - metabolism; Atherosclerosis - pathology; Bioinformatics; Biological Transport; Cardiovascular diseases; CD36 antigen; Cholesterol; Cholesterol - blood; Gene Expression Regulation; Heart diseases; Humans; Inflammation; Inflammation Mediators - metabolism; Interleukin 6; Lipids; Lipoproteins, LDL - pharmacology; Low density lipoprotein; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Macrophages - pathology; MicroRNAs - genetics; MicroRNAs - metabolism; miR‐342‐3p; Monocytes; NEAT1; oxidized low‐density lipoprotein (ox‐LDL); Prostaglandin endoperoxide synthase; Proteins; Ribonucleic acid; RNA; RNA Interference; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; siRNA; THP-1 Cells; Time dependence; Transfection; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumors
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.27340

Atherosclerosis has been recognized as a chronic inflammation process induced by lipid of the vessel wall. Oxidized low‐density lipoprotein (ox‐LDL) can drive atherosclerosis progression involving macrophages. Recently, long noncoding RNAs (lncRNAs) have been reported to play critical roles in atherosclerosis development. In our current study, we focused on the biological roles of lncRNA NEAT1 in atherosclerosis progress. Here, we found that ox‐LDL was able to trigger human macrophages THP‐1 cells, a human monocytic cell line, apoptosis in a dose‐dependent and time‐dependent course. In addition, we observed that NEAT1 was significantly increased in THP‐1 cells incubated with ox‐LDL and meanwhile miR‐342‐3p was greatly decreased. Then, NEAT1 was silenced by transfection of small interfering RNA (siRNA) of NEAT1 into THP‐1 cells. As exhibited, CD36, oil‐red staining levels, total cholesterol (TC), total cholesterol (TG) levels and THP‐1 cell apoptosis were obviously repressed by knockdown of NEAT1. Furthermore, inhibition of NEAT1 contributed to the repression of inflammation in vitro. Interleukin 6 (IL‐6), IL‐1β, cyclooxygenase‐2 (COX‐2) and tumour necrosis factor‐alpha (TNF‐α) protein levels were remarkably depressed by NEAT1 siRNA in THP‐1 cells. By using bioinformatics analysis, miR‐342‐3p was predicted as a downstream target of NEAT1 and the correlation between them was confirmed in our study. Moreover, overexpression of miR‐342‐3p could also greatly suppress inflammation response and lipid uptake in THP‐1 cells. Knockdown of NEAT1 and miR‐342‐3p mimics inhibited lipid uptake in THP‐1 cells. In conclusion, we implied that blockade of NEAT1 repressed inflammation response through modulating miR‐342‐3p in human macrophages THP‐1 cells and NEAT1 may offer a promising strategy to treat atherosclerotic cardiovascular diseases. We exhibited that NEAT1 silence and miR‐342‐3p overexpression suppressed inflammation release and lipid uptake in THP‐1 cells. We suggested that NEAT1 can act as a novel biomarker in atherosclerosis via targeting miR‐342‐3p in vitro.