Generic placeholder image

Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

General Research Article

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

Author(s): Jiaqi Yang, Xuze Lin , Liangshan Wang, Tienan Sun, Qi Zhao, Qian Ma* and Yujie Zhou*

Volume 18, Issue 6, 2020

Page: [652 - 662] Pages: 11

DOI: 10.2174/1570161118666200317153124

Price: $65

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.

Keywords: Autophagy, MALAT1, LC-3, macrophages, SIRT1, MAPK, NF-κB.

Graphical Abstract

[1]
Cannon B. Cardiovascular disease: Biochemistry to behaviour. Nature 2013; 493(7434): S2-3.
[http://dx.doi.org/10.1038/493S2a] [PMID: 23364768]
[2]
Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011; 473(7347): 317-25.
[http://dx.doi.org/10.1038/nature10146] [PMID: 21593864]
[3]
Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol 2013; 13(10): 709-21.
[http://dx.doi.org/10.1038/nri3520] [PMID: 23995626]
[4]
Jeong SJ, Lee MN, Oh GT. The Role of Macrophage Lipophagy in Reverse Cholesterol Transport. Endocrinol Metab (Seoul) 2017; 32(1): 41-6.
[http://dx.doi.org/10.3803/EnM.2017.32.1.41] [PMID: 28345315]
[5]
Razani B, Feng C, Coleman T, et al. Autophagy links inflammasomes to atherosclerotic progression. Cell Metab 2012; 15(4): 534-44.
[http://dx.doi.org/10.1016/j.cmet.2012.02.011] [PMID: 22440612]
[6]
Quinn JJ, Chang HY. Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet 2016; 17(1): 47-62.
[http://dx.doi.org/10.1038/nrg.2015.10] [PMID: 26666209]
[7]
Nagano T, Fraser P. No-nonsense functions for long noncoding RNAs. Cell 2011; 145(2): 178-81.
[http://dx.doi.org/10.1016/j.cell.2011.03.014] [PMID: 21496640]
[8]
Shen L, Chen L, Wang Y, Jiang X, Xia H, Zhuang Z. Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer. J Neurooncol 2015; 121(1): 101-8.
[http://dx.doi.org/10.1007/s11060-014-1613-0] [PMID: 25217850]
[9]
Hu J, Zhang L, Mei Z, et al. Interaction of E3 Ubiquitin Ligase MARCH7 with Long Noncoding RNA MALAT1 and Autophagy-Related Protein ATG7 Promotes Autophagy and Invasion in Ovarian Cancer. Cell Physiol Biochem 2018; 47(2): 654-66.
[http://dx.doi.org/10.1159/000490020] [PMID: 29794480]
[10]
Hirata H, Hinoda Y, Shahryari V, et al. Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205. Cancer Res 2015; 75(7): 1322-31.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-2931] [PMID: 25600645]
[11]
Wu Q, Yi X. Down-regulation of Long Noncoding RNA MALAT1 Protects Hippocampal Neurons Against Excessive Autophagy and Apoptosis via the PI3K/Akt Signaling Pathway in Rats with Epilepsy. J Mol Neurosci 2018; 65(2): 234-45.
[http://dx.doi.org/10.1007/s12031-018-1093-3] [PMID: 29858824]
[12]
Guo X, Wu X, Han Y, Tian E, Cheng J. LncRNA MALAT1 protects cardiomyocytes from isoproterenol-induced apoptosis through sponging miR-558 to enhance ULK1-mediated protective autophagy. J Cell Physiol 2019; 234(7): 10842-54.
[http://dx.doi.org/10.1002/jcp.27925] [PMID: 30536615]
[13]
Sun Y, Liu XL, Zhang D, et al. Platelet-Derived Exosomes Affect the Proliferation and Migration of Human Umbilical Vein Endothelial Cells Via miR-126. Curr Vasc Pharmacol 2019; 17(4): 379-87.
[http://dx.doi.org/10.2174/1570161116666180313142139] [PMID: 29532758]
[14]
Niu Y, Shao Z, Wang H, et al. LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling. Sci Rep 2016; 6: 26112.
[http://dx.doi.org/10.1038/srep26112] [PMID: 27181092]
[15]
Liao X, Sluimer JC, Wang Y, et al. Macrophage autophagy plays a protective role in advanced atherosclerosis. Cell Metab 2012; 15(4): 545-53.
[http://dx.doi.org/10.1016/j.cmet.2012.01.022] [PMID: 22445600]
[16]
Lavandero S, Troncoso R, Rothermel BA, Martinet W, Sadoshima J, Hill JA. Cardiovascular autophagy: concepts, controversies, and perspectives. Autophagy 2013; 9(10): 1455-66.
[http://dx.doi.org/10.4161/auto.25969] [PMID: 23959233]
[17]
Shao BZ, Han BZ, Zeng YX, Su DF, Liu C. The roles of macrophage autophagy in atherosclerosis. Acta Pharmacol Sin 2016; 37(2): 150-6.
[http://dx.doi.org/10.1038/aps.2015.87] [PMID: 26750103]
[18]
Ruiz-León AM, Lapuente M, Estruch R, Casas R. Clinical Advances in Immunonutrition and Atherosclerosis: A Review. Front Immunol 2019; 10: 837.
[http://dx.doi.org/10.3389/fimmu.2019.00837] [PMID: 31068933]
[19]
Abdulle LE, Hao JL, Pant OP, et al. MALAT1 as a Diagnostic and Therapeutic Target in Diabetes-Related Complications: A Promising Long-Noncoding RNA. Int J Med Sci 2019; 16(4): 548-55.
[http://dx.doi.org/10.7150/ijms.30097] [PMID: 31171906]
[20]
Li M, Duan L, Li Y, Liu B. Long noncoding RNA/circular noncoding RNA-miRNA-mRNA axes in cardiovascular diseases. Life Sci 2019.233116440
[http://dx.doi.org/10.1016/j.lfs.2019.04.066] [PMID: 31047893]
[21]
Skuratovskaia D, Vulf M, Komar A, Kirienkova E, Litvinova L. Promising Directions in Atherosclerosis Treatment Based on Epigenetic Regulation Using MicroRNAs and Long Noncoding RNAs. Biomolecules 2019; 9(6): 9.
[http://dx.doi.org/10.3390/biom9060226] [PMID: 31212708]
[22]
Zhang H, Zhao Z, Pang X, et al. Genistein Protects Against Ox-LDL-Induced Inflammation Through MicroRNA-155/SOCS1-Mediated Repression of NF-ĸB Signaling Pathway in HUVECs. Inflammation 2017; 40(4): 1450-9.
[http://dx.doi.org/10.1007/s10753-017-0588-3] [PMID: 28550396]
[23]
Song TF, Huang LW, Yuan Y, et al. LncRNA MALAT1 regulates smooth muscle cell phenotype switch via activation of autophagy. Oncotarget 2017; 9(4): 4411-26.
[PMID: 29435112]
[24]
Li S, Pan X, Yang S, et al. LncRNA MALAT1 promotes oxidized low-density lipoprotein-induced autophagy in HUVECs by inhibiting the PI3K/AKT pathway. J Cell Biochem 2019; 120(3): 4092-101.
[http://dx.doi.org/10.1002/jcb.27694] [PMID: 30485490]
[25]
Ma Z, Zhang J, Xu X, et al. LncRNA expression profile during autophagy and Malat1 function in macrophages. PLoS One 2019; 14(8): e0221104.
[http://dx.doi.org/10.1371/journal.pone.0221104] [PMID: 31425535]
[26]
Zhong S, Li L, Shen X, et al. An update on lipid oxidation and inflammation in cardiovascular diseases. Free Radic Biol Med 2019; 144: 266-78.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.03.036] [PMID: 30946962]
[27]
Mukhopadhyay S, Panda PK, Sinha N, Das DN, Bhutia SK. Autophagy and apoptosis: where do they meet? Apoptosis 2014; 19(4): 555-66.
[http://dx.doi.org/10.1007/s10495-014-0967-2] [PMID: 24415198]
[28]
Dodson M, Darley-Usmar V, Zhang J. Cellular metabolic and autophagic pathways: traffic control by redox signaling. Free Radic Biol Med 2013; 63: 207-21.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.05.014] [PMID: 23702245]
[29]
Wirawan E, Lippens S, Vanden Berghe T, et al. Beclin1: a role in membrane dynamics and beyond. Autophagy 2012; 8(1): 6-17.
[http://dx.doi.org/10.4161/auto.8.1.16645] [PMID: 22170155]
[30]
Kale J, Osterlund EJ, Andrews DW. BCL-2 family proteins: changing partners in the dance towards death. Cell Death Differ 2018; 25(1): 65-80.
[http://dx.doi.org/10.1038/cdd.2017.186] [PMID: 29149100]
[31]
Tsukahara S, Yamamoto S. tin-tin-win-shwe Inhalation of low-level formaldehyde increases the Bcl-2/Bax expression ratio in the hippocampus of immunologically sensitized mice. Neuroimmunomodulation 2006; 13(2): 63-8.
[http://dx.doi.org/10.1159/000094829] [PMID: 16888403]
[32]
Kaufmann A, Beier V, Franquelim HG, Wollert T. Molecular mechanism of autophagic membrane-scaffold assembly and disassembly. Cell 2014; 156(3): 469-81.
[http://dx.doi.org/10.1016/j.cell.2013.12.022] [PMID: 24485455]
[33]
Gast M, Rauch BH, Nakagawa S, et al. Immune system-mediated atherosclerosis caused by deficiency of long non-coding RNA MALAT1 in ApoE-/-mice. Cardiovasc Res 2019; 115(2): 302-14.
[http://dx.doi.org/10.1093/cvr/cvy202] [PMID: 30101304]
[34]
Lee SI, Min KS, Bae WJ, et al. Role of SIRT1 in heat stress- and lipopolysaccharide-induced immune and defense gene expression in human dental pulp cells. J Endod 2011; 37(11): 1525-30.
[http://dx.doi.org/10.1016/j.joen.2011.07.006] [PMID: 22000456]
[35]
Sathyanarayan A, Mashek MT, Mashek DG. ATGL Promotes Autophagy/Lipophagy via SIRT1 to Control Hepatic Lipid Droplet Catabolism. Cell Rep 2017; 19(1): 1-9.
[http://dx.doi.org/10.1016/j.celrep.2017.03.026] [PMID: 28380348]
[36]
Song YM, Lee YH, Kim JW, et al. Metformin alleviates hepatosteatosis by restoring SIRT1-mediated autophagy induction via an AMP-activated protein kinase-independent pathway. Autophagy 2015; 11(1): 46-59.
[http://dx.doi.org/10.4161/15548627.2014.984271] [PMID: 25484077]
[37]
Yang QB, He YL, Zhong XW, Xie WG, Zhou JG. Resveratrol ameliorates gouty inflammation via upregulation of sirtuin 1 to promote autophagy in gout patients. Inflammopharmacology 2019; 27(1): 47-56.
[http://dx.doi.org/10.1007/s10787-018-00555-4] [PMID: 30600470]
[38]
Gordon JW, Shaw JA, Kirshenbaum LA. Multiple facets of NF-κB in the heart: to be or not to NF-κB. Circ Res 2011; 108(9): 1122-32.
[http://dx.doi.org/10.1161/CIRCRESAHA.110.226928] [PMID: 21527742]
[39]
Nadtochiy SM, Redman E, Rahman I, Brookes PS. Lysine deacetylation in ischaemic preconditioning: the role of SIRT1. Cardiovasc Res 2011; 89(3): 643-9.
[http://dx.doi.org/10.1093/cvr/cvq287] [PMID: 20823277]
[40]
Yeung F, Hoberg JE, Ramsey CS, et al. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 2004; 23(12): 2369-80.
[http://dx.doi.org/10.1038/sj.emboj.7600244] [PMID: 15152190]
[41]
Alcendor RR, Kirshenbaum LA, Imai S, Vatner SF, Sadoshima J. Silent information regulator 2alpha, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes. Circ Res 2004; 95(10): 971-80.
[http://dx.doi.org/10.1161/01.RES.0000147557.75257.ff] [PMID: 15486319]
[42]
Alcendor RR, Gao S, Zhai P, et al. Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res 2007; 100(10): 1512-21.
[http://dx.doi.org/10.1161/01.RES.0000267723.65696.4a] [PMID: 17446436]
[43]
Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME. Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. Science 1999; 286(5443): 1358-62.
[http://dx.doi.org/10.1126/science.286.5443.1358] [PMID: 10558990]
[44]
Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature 2001; 410(6824): 37-40.
[http://dx.doi.org/10.1038/35065000] [PMID: 11242034]
[45]
Cowan KJ, Storey KB. Mitogen-activated protein kinases: new signaling pathways functioning in cellular responses to environmental stress. J Exp Biol 2003; 206(Pt 7): 1107-15.
[http://dx.doi.org/10.1242/jeb.00220] [PMID: 12604570]
[46]
Wang J, Xu N, Feng X, et al. Targeted disruption of Smad4 in cardiomyocytes results in cardiac hypertrophy and heart failure. Circ Res 2005; 97(8): 821-8.
[http://dx.doi.org/10.1161/01.RES.0000185833.42544.06] [PMID: 16151019]
[47]
Han Y, Wu Z, Wu T, et al. Tumor-suppressive function of long noncoding RNA MALAT1 in glioma cells by downregulation of MMP2 and inactivation of ERK/MAPK signaling. Cell Death Dis 2016. 7e2123
[http://dx.doi.org/10.1038/cddis.2015.407] [PMID: 26938295]
[48]
Wang Y, Wang X, Sun M, Zhang Z, Cao H, Chen X. NF-kB activity-dependent P-selectin involved in ox-LDL-induced foam cell formation in U937 cell. Biochem Biophys Res Commun 2011; 411(3): 543-8.
[http://dx.doi.org/10.1016/j.bbrc.2011.06.177] [PMID: 21763287]
[49]
Cominacini L, Anselmi M, Garbin U, et al. Enhanced plasma levels of oxidized low-density lipoprotein increase circulating nuclear factor-kappa B activation in patients with unstable angina. J Am Coll Cardiol 2005; 46(5): 799-806.
[http://dx.doi.org/10.1016/j.jacc.2005.05.063] [PMID: 16139128]
[50]
Luo Y, Lu S, Ai Q, et al. SIRT1/AMPK and Akt/eNOS signaling pathways are involved in endothelial protection of total aralosides of Aralia elata (Miq) Seem against high-fat diet-induced atherosclerosis in ApoE-/- mice. Phytother Res 2019; 33(3): 768-78.
[http://dx.doi.org/10.1002/ptr.6269] [PMID: 30637828]
[51]
Zhu Z, Li J, Zhang X. Salidroside protects against ox-LDL-induced endothelial injury by enhancing autophagy mediated by SIRT1-FoxO1 pathway. BMC Complement Altern Med 2019; 19(1): 111.
[http://dx.doi.org/10.1186/s12906-019-2526-4] [PMID: 31146723]
[52]
Ziaei S, Halaby R. Immunosuppressive, anti-inflammatory and anti-cancer properties of triptolide: A mini review. Avicenna J Phytomed 2016; 6(2): 149-64.
[PMID: 27222828]
[53]
Wen HL, Liang ZS, Zhang R, Yang K. Anti-inflammatory effects of triptolide improve left ventricular function in a rat model of diabetic cardiomyopathy. Cardiovasc Diabetol 2013; 12: 50.
[http://dx.doi.org/10.1186/1475-2840-12-50] [PMID: 23530831]
[54]
Luo L, Yang T. Triptolide inhibits the progression of atherosclerosis in apolipoprotein E-/- mice. Exp Ther Med 2016; 12(4): 2307-13.
[http://dx.doi.org/10.3892/etm.2016.3619] [PMID: 27698729]
[55]
Yao P, Li Y, Yang Y, Yu S, Chen Y. Triptolide improves cognitive dysfunction in rats with vascular dementia by activating the SIRT1/PGC-1α signaling pathway. Neurochem Res 2019; 44(8): 1977-85.
[http://dx.doi.org/10.1007/s11064-019-02831-3] [PMID: 31236795]
[56]
Wei YM, Wang YH, Xue HQ, Luan ZH, Liu BW, Ren JH. Triptolide, A Potential Autophagy Modulator. Chin J Integr Med 2019; 25(3): 233-40.
[http://dx.doi.org/10.1007/s11655-018-2847-z] [PMID: 30178091]
[57]
Li XY, Wang SS, Han Z, et al. Triptolide Restores Autophagy to Alleviate Diabetic Renal Fibrosis through the miR-141-3p/PTEN/Akt/mTOR Pathway. Mol Ther Nucleic Acids 2017; 9: 48-56.
[http://dx.doi.org/10.1016/j.omtn.2017.08.011] [PMID: 29246323]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy