Title:LncRNA MALAT1 Enhances ox-LDL-Induced Autophagy through the SIRT1/MAPK/NF-κB Pathway in Macrophages
VOLUME: 18 ISSUE: 6
Author(s):Jiaqi Yang, Xuze Lin , Liangshan Wang, Tienan Sun, Qi Zhao, Qian Ma* and Yujie Zhou*
Affiliation:Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029
Keywords:Autophagy, MALAT1, LC-3, macrophages, SIRT1, MAPK, NF-κB.
Abstract: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.
