NEAT1 contributes to ox‐LDL‐induced inflammation and oxidative stress in macrophages through inhibiting miR‐128

Abstract

Long noncoding RNAs (lncRNA) have been recognized as significant regulators in the progression of atherosclerosis (AS). Oxidized low-density lipoprotein (ox-LDL) can induce macrophage inflammation and oxidative stress, that serves important roles in AS. However, the exact function of lncRNA NEAT1 and its possible molecular mechanism in AS remain unclear. Here, we concentrated on the roles and molecular mechanisms of NEAT1 in AS development. In our current study, we observed that NEAT1 was elevated by ox-LDL in a dose-dependent and time-dependent manner. RAW264.7 cell survival was greatly enhanced, and cell apoptosis was significantly inhibited by LV-shNEAT1 transfection. In addition, knockdown of NEAT1 in RAW264.7 cells repressed CD36 expression and foam cell formation while NEAT1 overexpression shown an opposite process. Moreover, NEAT1 downregulation inhibited inflammation molecules including IL-6, IL-1β, and TNF-α. Meanwhile, silencing of NEAT1 can also suppress reactive oxygen species (ROS) and malondialdehyde (MDA) levels with an enhancement of superoxide dismutase (SOD) activity in RAW264.7 cells. MicroRNAs are some short RNAs, and they can regulate multiple biological functions in many diseases including AS. Here, we found that miR-128 expression was remarkably decreased in ox-LDL-incubated RAW264.7 cells. Interestingly, miR-128 mimics was able to reverse AS-correlated events induced by overexpression of NEAT1. By using bioinformatics analysis, miR-128 was predicted as a target of NEAT1 and the correlation between them was validated in our study. Taken these together, it was implied that NEAT1 participated in ox-LDL-induced inflammation and oxidative stress in AS development through sponging miR-128.

Silencing of MEG3 inhibited ox‐LDL‐induced inflammation and apoptosis in macrophages via modulation of the MEG3/miR‐204/CDKN2A regulatory axis

“…LncRNAs affect the physiological and pathological progression of a variety of human diseases, including diabetic nephropathy, autoimmune diseases, immune-related diseases, neurodegenerative diseases, human cancers, metabolic diseases, and cardiovascular-related diseases (Adams et al, 2017;Chen et al, 2017;Haemmig et al, 2017;Rogoyski et al, 2017). Reports have demonstrated that NEAT1 contributes to ox-LDL-induced inflammation and oxidative stress in macrophages (Chen et al, 2018). Reports have demonstrated that NEAT1 contributes to ox-LDL-induced inflammation and oxidative stress in macrophages (Chen et al, 2018).…”

“…Recent research has demonstrated that several lncRNAs, including UCA1, MALAT1, TUG1, NEAT1, HOTAIR, DIGIT, H19, and MEG3, play important roles in AS (Liu et al, 2017a, b;Sallam et al, 2018;Yu and Wang, 2018). Reports have demonstrated that NEAT1 contributes to ox-LDL-induced inflammation and oxidative stress in macrophages (Chen et al, 2018). However, although increasing research has focused on the effects of lncRNAs in macrophages treated with ox-LDL, there is a need to further understand the related roles and underlying mechanisms.…”

Transcription Factor FOXK1 Regulates the lncRNA NEAT1 to Promote Glioma Development Through Mediating KDM3A

“…NEAT1 has been shown to be highly expressed in gliomas, and its high expression is a risk factor for the prognosis of glioma patients [23]. At the same time, we found that in atherosclerosis induced by oxidized low-density lipoprotein (ox-LDL), NEAT1 participates in the in ammatory response and oxidative stress through competing with miR-128 [24]. MiR-128 has been con rmed to inhibit glioma cell proliferation and differentiation and promote glioma cell apoptosis [25,26].…”

Downregulation of long non-coding RNA nuclear enriched abundant transcript 1 promotes cell proliferation and inhibits cell apoptosis by targeting miR-193a in myocardial ischemia/reperfusion injury

“…***p < 0.001, OGD/R&sh-NC group vs. Normal&sh-NC group; **p < 0.01, OGD/R&sh-NC group vs. Normal&sh-NC group; ##p < 0.01, OGD/R&sh-NEAT1 group vs. OGD/R&sh-NC group resolving actions in order to remove inflammatory leucocytes during postinfarction inflammation [22]. For lnc-NEAT1, one study shows that lnc-NEAT1 presents higher expression in neutrophils compared to other immune cells and lnc-NEAT1 may derive from metastatic tissues and neutrophils, meanwhile, lnc-NEAT1 promotes ox-LDL-induced inflammation and oxidative stress in macrophages [23,24]. Although these previous studies reveal that lnc-NEAT1 serves as an oncogene in various cancers through promoting cell proliferation and inhibiting cell apoptosis, moreover, lnc-NEAT1 may present influences in neutrophils and macrophages, which are inflammatory cells involved in the myocardial I/R injury, little is known about the effect of lnc-NEAT1 on cells activities in cardiovascular diseases, particularly myocardial I/R injury.…”