LncRNA MALAT1 Enhances ox-LDL-Induced Autophagy through the SIRT1/MAPK/NF-κB Pathway in Macrophages

• Published in: Current vascular pharmacology Vol. 18; no. 6; p. 652
• Main Authors: Yang, Jiaqi, Lin, Xuze, Wang, Liangshan, Sun, Tienan, Zhao, Qi, Ma, Qian, Zhou, Yujie
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2020
• Subjects: Apoptosis - drug effects; Autophagy - drug effects; Beclin-1 - genetics; Beclin-1 - metabolism; Foam Cells - drug effects; Foam Cells - metabolism; Foam Cells - ultrastructure; Humans; Lipoproteins, LDL - toxicity; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Mitogen-Activated Protein Kinases - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; THP-1 Cells; Transcription Factor RelA - metabolism; NF-κB; macrophages; MALAT1; MAPK; Autophagy; SIRT1; LC-3
• ISSN: 1875-6212
• DOI: 10.2174/1570161118666200317153124

Atherosclerosis is the main cause of cardiovascular and cerebrovascular diseases. In advanced atherosclerotic plaque, macrophage apoptosis coupled with inflammatory cytokine secretion promotes the formation of necrotic cores. It has also been demonstrated that the long-noncoding Ribonucleic Acid (lnc RNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), with its potent function on gene transcription modulation, maintains oxidized low-density lipoprotein (ox-LDL)- induced macrophage autophagy (i.e., helps with cholesterol efflux). It also showed that MALAT1 activated Sirtuin 1 (SIRT1), which subsequently inhibited the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways. ox-LDL has been used to incubate human myeloid leukemia mononuclear cells (THP-1)-derived macrophages to establish an in vitro foam cell model. Quantitative reverse-transcription polymerase chain reaction and Western blot analyses confirmed the increased expression level of MALAT1 and the autophagy-related protein Microtubuleassociated protein light chain 3 (LC-3), beclin-1. The small interfering RNA study showed a significant decrease in autophagy activity and an increase in apoptotic rate when knocking down MALAT1. Further study demonstrated that MALAT1 inhibited the expression of MAPK and NF-κB (p65) by upregulating SIRT1.