Long non‑coding RNA MALAT1 regulates cholesterol accumulation in ox‑LDL‑induced macrophages via the microRNA‑17‑5p/ABCA1 axis

Abstract

atherosclerosis (aS), a major cause of cardiovascular disease, has developed into a serious challenge to the health system. The long non-coding rna (lncrna) metastasis associated lung adenocarcinoma transcript 1 (MalaT1) is associated with the pathogenesis of aS. However, whether MalaT1 can affect cholesterol accumulation in macrophages during aS progression, and the potential molecular mechanism involved in this progression have not been elucidated. in the present study, the mrna expression level of MalaT1 was measured using reverse transcription-quantitative Pcr (rT-qPcr) and the protein expression level was detected via western blot analysis. oil red o staining was used for detecting lipid accumulation in macrophages. Bioinformatics, dual-luciferase reporter and rT-qPcr assays were used to investigate the relationship between MalaT1 and the microrna (mir)-17-5p/aTP-binding cassette transporter a1 (aBca1) axis. The present results suggested that the MALAT1 expression level was significantly decreased in patients with aS and in oxidized low-density lipoprotein (ox-ldl)-stimulated macrophages. Knockdown of MalaT1 increased ox-ldl uptake, lipid accumulation and the total cholesterol (T-cHo) level in ox-ldl-induced macrophages. in addition, MalaT1 inhibition significantly decreased the mrna and protein expression levels of scavenger receptor (Sr) class B member 1, apolipoprotein e (apoe) and aBca1. However, MalaT1 increased the expression level of Sr class a. Subsequently, the present study investigated whether MalaT1 could target mir-17-5p to regulate the expression level of aBca1, which is involved in cholesterol efflux from macrophages. The present results suggested that inhibition of mir-17-5p reversed the effects of MalaT1 knockdown on T-cHo content, and protein expression levels of apoe and aBca1 in ox-ldl-stimulated macrophages. in summary, knockdown of MalaT1 may promote cholesterol accumulation by regulating the mir-17-5p/aBca1 axis in ox-ldl-induced THP-1 macrophages.

Long-non Coding RNAs Related to Fat Deposition in Pigs Included lncRNA Corresponding to Human MALAT1

“…Earlier report Yan et al [36] suggested that MALAT1 promotes hepatic steatosis by increased stability of SREBP-1c protein. Liu et al [37] presented that it is involved in regulating cholesterol accumulation in ox-LDL-induced macrophages via microRNA-17-5p/ABCA1 axis. The study analysed MALAT1, and TUG1 expression in AT in the obesity context showed no differences between obese and normal women, but MALAT1 mRNA level in SAT was positively correlated with SREBP-1c, PPARγ, and their targets; FAS and ACACA, as well as with VAT mRNA levels of PGC1α [38].…”

PPARγ Transcription Deficiency Exacerbates High-Fat Diet-Induced Adipocyte Hypertrophy and Insulin Resistance in Mice

“…Serum insulin level was determined by ELISA using an ultra-sensitive mouse insulin kit (Crystal Chem, USA) ( Ding et al., 2016 ). Serum levels of total cholesterol, triglycerides, LDL-C, HDL-C, and free fatty acids (FFA) levels were assayed using the calorimetric kits from Nanjing Jiancheng Bioengineering Institute (Nanjing, China) ( Jiang et al., 2016 ; Wang et al., 2019 ; Liu et al., 2020 ). Liver TG was analyzed using Tissue triglyceride assay kit (Applygen, Beijing, China) ( Wang C. et al., 2016 ).…”

Long non‐coding RNA MALAT1 and its target microRNA‐125b associate with disease risk, severity, and major adverse cardiovascular event of coronary heart disease

“…5,6 Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) is recognized as a biomarker in various cancers, and recent studies indicate that it is also involved in the pathogenesis of atherosclerosis. [7][8][9][10] Mechanically, lncRNA MALAT1 silencing attenuates oxidized low-density lipoprotein (ox-LDL)-induced endothelial inflammation and protects the endothelium from oxidative stress, further affecting the progression of atherosclerosis. 7 Additionally, another study indicates that lncRNA MALAT1 affects lipid metabolism disorder and is associated with inflammation response as well as the pathological progression of atherosclerosis via regulating ox-LDL-related macrophages.…”

“…7 Additionally, another study indicates that lncRNA MALAT1 affects lipid metabolism disorder and is associated with inflammation response as well as the pathological progression of atherosclerosis via regulating ox-LDL-related macrophages. 8 Furthermore, lncRNA MALAT1 is reported to regulate cardiac inflammation and promote acute myocardial infarction via interaction of microRNA-125b (miR-125b), and miR-125b serves as a pathogenic mediator in multiple vascular diseases. [11][12][13] For example, miR-125b attenuates endothelin-1 expression, suppresses vascular endothelial-cadherin mRNA translation, and reduces endothelial permeability, involving the development of atherosclerosis.…”