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

Abstract

Atherosclerosis (AS) is one of the most common chronic inflammatory diseases and a major cause of morbidity and mortality. However, the underlying molecular mechanisms of the progression of AS are still largely unknown. Increasing evidence has demonstrated that long noncoding RNAs (lncRNAs) play important roles in a variety of biological processes and the physiological and pathological progression of human diseases. In this study, we aimed to explore the role and underlying molecular mechanism of lncRNA MEG3 in Raw264.7 cells treated with oxidized low-density lipoprotein (ox-LDL). First, we found that ox-LDL inhibited the cell viability and proliferation, increased TNFa and IL1b secretion and induced the apoptosis of Raw264.7 cells. Second, we demonstrated that ox-LDL upregulated MEG3 expression and that knockdown of MEG3 inhibited the action of ox-LDL in Raw264.7 cells. Third, we showed that MEG3 sponged miR-204 in Raw264.7 cells treated with ox-LDL. Fourth, we demonstrated that miR-204 regulated the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A) in Raw264.7 cells treated with ox-LDL. Finally, we revealed that MEG3 exerted its function via the regulation of the MEG3/miR-204/CDKN2A regulatory axis in Raw264.7 cells treated with ox-LDL. In summary, our study identified the role of the MEG3/miR-204/CDKN2A pathway in Raw264.7 cells treated with ox-LDL, revealed a novel regulatory pathway in AS and indicated potential novel characteristic biomarkers and therapeutic targets for AS.

Expression level and diagnostic value of exosomal NEAT1/miR‐204/MMP‐9 in acute ST‐segment elevation myocardial infarction

“…miR-204 is a small single stranded non-coding RNA molecule that can inhibit apoptosis, autophagy, 35 and inflammatory factors. 36 In the present study, miR-204 expression was significantly decreased in serum exosomes of patients with STEMI, but no significant change was observed in the UA group. After analysis of clinical data, we found that LDL-C was higher in the STEMI group, which may promote more conversion of LDL-C to ox-LDL, further inhibiting miR-204, and leading to a significant decrease in miR-204 in the STEMI group.…”

“…miR‐204 inhibition of MMP‐9 affects cell invasion, 16 suggesting that NEAT1 may further enhance MMP‐9 activity by inhibiting miR‐204 expression. miR‐204 is a small single stranded non‐coding RNA molecule that can inhibit apoptosis, autophagy, 35 and inflammatory factors 36 . In the present study, miR‐204 expression was significantly decreased in serum exosomes of patients with STEMI, but no significant change was observed in the UA group.…”

Retracted: Long noncoding RNA MEG3 deteriorates inflammatory damage by downregulating microRNA‐101a

“…Increasing studies reflected lncRNAs exert their effect by regulating miRNAs. For instance, Yan et al reflected a si‐MEG3 played protective effect in inflammatory damage by miR‐204. Wang et al also reflected MEG3 worked in inflammatory damage by miR‐203.…”

Long Non-Coding RNAs Link Oxidized Low-Density Lipoprotein With the Inflammatory Response of Macrophages in Atherogenesis

“…It was shown that MEG3 enhanced pyroptosis, a highly inflammatory form of programmed cell death, in ox-LDL treated HCAECs by sponging miR-223 targeting NOD-like receptor protein 3 (NLRP3) (85,114). Consistently, MEG3 was upregulated in ox-LDL treated RAW264.7 cells and increased secretion of TNF-α and IL1β by sponging miR-204, which targeted the cyclin-dependent kinase inhibitor 2A (CDKN2A) (86). Thus, MEG3 promotes the development of atherosclerosis by enhancing EC dysfunction and inflammation.…”