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

Abstract

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. K E Y W O R D S atherosclerosis, miR-342-3p, NEAT1, oxidized low-density lipoprotein (ox-LDL)

Long Non-coding RNA NEAT1 Alleviates Acute-on-Chronic Liver Failure Through Blocking TRAF6 Mediated Inflammatory Response

“…LncRNAs are pivotal regulators of gene functions and various cellular processes (Wang et al, 2018Yamazaki et al, 2018). The lncRNAs have been found to be involved in subcellular architecture, protein complex stabilization, as well as in physiology and pathophysiology (Del Vecchio et al, 2018;Gutschner et al, 2018;Liu et al, 2018;Wang et al, 2019;Yan et al, 2019;Yu et al, 2019). Within the last few years, numerous studies have shown that nuclear enriched abundant transcript 1 (NEAT1) play crucial roles both in carcinogenesis and non-cancerous diseases such as neurodegeneration and inflammation .…”

Long noncoding RNA NEAT1 correlates with higher disease risk, worse disease condition, decreased miR‐124 and miR‐125a and predicts poor recurrence‐free survival of acute ischemic stroke

“…For example, a study shows that lncRNA NEAT1 is overexpressed in myocardial IR injury mice models and lncRNA NEAT1 knockdown represses levels of pro‐inflammatory cytokines (TNF‐α, IL‐1β, and IL‐6), decreases troponin level, reduces cardiocytes apoptosis, and inhibits release of lactate LDH in vitro . Besides, a study displays that lncRNA NEAT1 knockdown inhibits levels of IL‐6, IL‐1β, cyclooxygenase‐2 (COX‐2), and TNF‐α via regulating miR‐342‐3p in human macrophages THP‐1 cells . For stroke, a study discloses that lncRNA NEAT1 upregulation enhances OGD/R injury‐induced inflammatory response in cerebral microglial cells through Wnt/β‐catenin signaling pathway .…”

“…LncRNA NEAT1, as an abundant and ubiquitously expressed lncRNA, has been reported to be a pivotal factor in the pathology of various diseases, including cardiovascular and cerebrovascular diseases. [14][15][16] For example, a study shows that lncRNA NEAT1 is overexpressed in myocardial IR injury mice models and lncRNA NEAT1 knockdown represses levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), decreases troponin level, reduces cardiocytes apoptosis, and inhibits release of lactate LDH in vitro. 14 Besides, a study displays that lncRNA NEAT1 knockdown inhibits levels of IL-6, IL-1β, cyclooxygenase-2 (COX-2), and TNF-α via regulating miR-342-3p in human macrophages THP-1 cells.…”

“…14 Besides, a study displays that lncRNA NEAT1 knockdown inhibits levels of IL-6, IL-1β, cyclooxygenase-2 (COX-2), and TNF-α via regulating miR-342-3p in human macrophages THP-1 cells. 15 For stroke, a study discloses that lncRNA NEAT1 upregulation enhances OGD/R injury-induced inflammatory response in cerebral microglial cells through Wnt/β-catenin signaling pathway. 16 These studies reveal that lncRNA NEAT1 may promote the disease occurrence and enhance inflammation response via targeted genes or downstream signaling pathways in cardiovascular and cerebrovascular diseases.…”

“…12,13 Furthermore, the biological roles of lncRNA NEAT1 in cardiovascular and cerebrovascular diseases have been disclosed in some experiments, such as the promotion of lncRNA NEAT1 on inflammatory response in myocardial ischemia-reperfusion injury mice models and the inhibition of lncRNA NEAT1 knockdown on atherosclerosis-correlated events in vitro. 14,15 For stroke, previous study displays that lncRNA NEAT1 facilitates oxygen-glucose deprivation/reoxygenation (OGD/R) injury and neuroinflammation damage of microglial cells, meanwhile, lncRNA NEAT1 enhances intima thickening or vascular occlusion through modulating the phenotype conversion of vascular smooth muscle cells, together with excessive apoptosis of epithelial cells, indicating that lncRNA NEAT1 is a therapeutic target for ischemic stroke. 16,17 Based on these indications, we hypothesized that ln-cRNA NEAT1 might play a critical role in AIS development, progression, and prognosis, however, the related evidence was limited.…”