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10.01.2022 | Basic Science • Original Article

Long non-coding RNA MALAT1 affects intermittent hypoxia-induced endothelial injury by regulating miR-142-3p/HMGB1

verfasst von: Meng-Xue Chen, Li-Da Chen, Jian-Chai Huang, Ai-Ming Zeng, Jie-Feng Huang, Qi-Chang Lin

Erschienen in: Sleep and Breathing | Ausgabe 4/2022

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Abstract

Background

Obstructive sleep apnea (OSA) is a risk factor for atherosclerosis. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is strongly linked to endothelial cell functions. However, the function of MALAT1 in intermittent hypoxia (IH) associated vascular endothelial injury has not been explored yet. The current study makes great attempts to investigate the function of MALAT1 in IH-induced endothelial injury and its latent control network.

Methods

To mimic the effect of OSA, we cultured the human umbilical vein endothelial cells (HUVECs) under intermittent hypoxia. Western blot was applied to measure the expression level of associated proteins including capase-3, Bax, Bcl-2 while qRT-PCR was used in measurement of MALAT1 and miR-142-3p. Cell Counting Kit-8 (CCK-8) was carried out in assessing cell viability. Dual-luciferase reporter assay was applied to verify the relationships among high mobility group box (HMGB)1 and MALAT1, miR-142-3p.

Results

IH treatment significantly reduced cell viability but enhanced cell apoptosis in HUVECs. Concomitantly, MALAT1 was significantly upregulated in IH-treated HUVECs. Further experiment showed that MALAT1 knockdown augmented IH-induced injury of HUVECs. In addition, it was confirmed by dual-luciferase reporter assay that MALAT1 interacted with miR-142-3p directly. Besides, inhibition of miR-142-3p alleviated damage induced by MALAT1 knockdown in IH-treated HUVECs. Finally, miR-142-3p interacted with HMGB1 directly and inhibition of HMGB1 protein expression mediated by MALAT1 knockdown was reversed by miR-142-3p inhibitor.

Conclusions

IH resulted in increased expression of MALAT1 in HUVECs. MALAT1 knockdown augmented IH-induced injury of HUVECs. MALAT1 exerted its effects on IH-treated HUVECs via miR-142-3p/HMGB1.

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Gastaut H, Tassinari CA, Duron B (1966) Polygraphic study of the episodic diurnal and nocturnal (hypnic and respiratory) manifestations of the Pickwick syndrome. Brain Res 1(2):167–186CrossRefPubMed

Mooe T, Franklin KA, Holmstrom K, Rabben T, Wiklund U (2001) Sleep-disordered breathing and coronary artery disease: long-term prognosis. Am J Respir Crit Care Med 164(10 Pt 1):1910–1913. https://doi.org/10.1164/ajrccm.164.10.2101072CrossRefPubMed

Drager LF, Polotsky VY, Lorenzi-Filho G (2011) Obstructive sleep apnea: an emerging risk factor for atherosclerosis. Chest 140(2):534–542. https://doi.org/10.1378/chest.10-2223CrossRefPubMedPubMedCentral

Jun J, Reinke C, Bedja D, Berkowitz D, Bevans-Fonti S, Li J, Barouch LA, Gabrielson K, Polotsky VY (2010) Effect of intermittent hypoxia on atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis 209(2):381–386. https://doi.org/10.1016/j.atherosclerosis.2009.10.017CrossRefPubMed

Fletcher EC, Lesske J, Qian W, Miller CC 3rd, Unger T (1992) Repetitive, episodic hypoxia causes diurnal elevation of blood pressure in rats. Hypertension 19(6 Pt 1):555–561. https://doi.org/10.1161/01.hyp.19.6.555CrossRefPubMed

Philippi NR, Bird CE, Marcus NJ, Olson EB, Chesler NC, Morgan BJ (2010) Time course of intermittent hypoxia-induced impairments in resistance artery structure and function. Respir Physiol Neurobiol 170(2):157–163. https://doi.org/10.1016/j.resp.2009.12.003CrossRefPubMed

Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340(2):115–126. https://doi.org/10.1056/NEJM199901143400207CrossRefPubMed

Verma S, Anderson TJ (2002) Fundamentals of endothelial function for the clinical cardiologist. Circulation 105(5):546–549CrossRefPubMed

Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J, Veeravalli L, Ruan XA, Ruan YJ, Lassmann T, Carninci P, Brown JB, Lipovich L, Gonzalez JM, Thomas M, Davis CA, Shiekhattar R, Gingeras TR, Hubbard TJ, Notredame C, Harrow J, Guigo R (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22(9):1775–1789. https://doi.org/10.1101/gr.132159.111CrossRefPubMedPubMedCentral

10.

Quinn JJ, Chang HY (2016) Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet 17(1):47–62. https://doi.org/10.1038/nrg.2015.10CrossRefPubMed

11.

Lin C, Yang L (2018) Long noncoding RNA in cancer: wiring signaling circuitry. Trends Cell Biol 28(4):287–301. https://doi.org/10.1016/j.tcb.2017.11.008CrossRefPubMed

12.

Li H, Zhu H, Ge J (2016) Long noncoding RNA: recent updates in atherosclerosis. Int J Biol Sci 12(7):898–910. https://doi.org/10.7150/ijbs.14430CrossRefPubMedPubMedCentral

13.

DiStefano JK (2018) The emerging role of long noncoding RNAs in human disease. Methods Mol Biol 1706:91–110. https://doi.org/10.1007/978-1-4939-7471-9_6CrossRefPubMed

14.

Sigdel KR, Cheng A, Wang Y, Duan L, Zhang Y (2015) The emerging functions of long noncoding RNA in immune cells: autoimmune diseases. J Immunol Res 2015:848790. https://doi.org/10.1155/2015/848790CrossRefPubMedPubMedCentral

15.

Guo J, Liu Z, Gong R (2019) Long noncoding RNA: an emerging player in diabetes and diabetic kidney disease. Clin Sci (Lond) 133(12):1321–1339. https://doi.org/10.1042/CS20190372CrossRef

16.

Liu JY, Yao J, Li XM, Song YC, Wang XQ, Li YJ, Yan B, Jiang Q (2014) Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus. Cell Death Dis 5:e1506. https://doi.org/10.1038/cddis.2014.466CrossRefPubMedPubMedCentral

17.

Michalik KM, You X, Manavski Y, Doddaballapur A, Zornig M, Braun T, John D, Ponomareva Y, Chen W, Uchida S, Boon RA, Dimmeler S (2014) Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res 114(9):1389–1397. https://doi.org/10.1161/CIRCRESAHA.114.303265CrossRefPubMed

18.

Toffoli S, Roegiers A, Feron O, Van Steenbrugge M, Ninane N, Raes M, Michiels C (2009) Intermittent hypoxia is an angiogenic inducer for endothelial cells: role of HIF-1. Angiogenesis 12 (1):47–67. https://doi.org/10.1007/s10456-009-9131-y

19.

Tang D, Kang R, Cheh CW, Livesey KM, Liang X, Schapiro NE, Benschop R, Sparvero LJ, Amoscato AA, Tracey KJ, Zeh HJ, Lotze MT (2010) HMGB1 release and redox regulates autophagy and apoptosis in cancer cells. Oncogene 29(38):5299–5310. https://doi.org/10.1038/onc.2010.261CrossRefPubMedPubMedCentral

20.

Tuleta I, Franca CN, Wenzel D, Fleischmann B, Nickenig G, Werner N, Skowasch D (2014) Hypoxia-induced endothelial dysfunction in apolipoprotein E-deficient mice; effects of infliximab and L-glutathione. Atherosclerosis 236(2):400–410. https://doi.org/10.1016/j.atherosclerosis.2014.08.021CrossRefPubMed

21.

El Solh AA, Akinnusi ME, Baddoura FH, Mankowski CR (2007) Endothelial cell apoptosis in obstructive sleep apnea: a link to endothelial dysfunction. Am J Respir Crit Care Med 175(11):1186–1191. https://doi.org/10.1164/rccm.200611-1598OCCrossRefPubMed

22.

Ma L, Zhang J, Liu Y (2016) Roles and mechanisms of obstructive sleep apnea-hypopnea syndrome and chronic intermittent hypoxia in atherosclerosis: evidence and prospective. Oxid Med Cell Longev 2016:8215082. https://doi.org/10.1155/2016/8215082CrossRefPubMedPubMedCentral

23.

Chen Q, Lin G, Huang J, Chen G, Huang X, Lin Q (2019) Expression profile of long non-coding RNAs in rat models of OSA-induced cardiovascular disease: new insight into pathogenesis. Sleep breathing 23(3):795–804. https://doi.org/10.1007/s11325-018-1753-0CrossRefPubMed

24.

Arslan S, Berkan O, Lalem T, Ozbilum N, Goksel S, Korkmaz O, Cetin N, Devaux Y (2017) Long non-coding RNAs in the atherosclerotic plaque. Atherosclerosis 266:176–181. https://doi.org/10.1016/j.atherosclerosis.2017.10.012CrossRefPubMed

25.

Cremer S, Michalik KM, Fischer A, Pfisterer L, Jae N, Winter C, Boon RA, Muhly-Reinholz M, John D, Uchida S, Weber C, Poller W, Gunther S, Braun T, Li DY, Maegdefessel L, Perisic Matic L, Hedin U, Soehnlein O, Zeiher A, Dimmeler S (2019) Hematopoietic deficiency of the long noncoding RNA MALAT1 promotes atherosclerosis and plaque inflammation. Circulation 139(10):1320–1334. https://doi.org/10.1161/CIRCULATIONAHA.117.029015CrossRefPubMed

26.

Xin JW, Jiang YG (2017) Long noncoding RNA MALAT1 inhibits apoptosis induced by oxygen-glucose deprivation and reoxygenation in human brain microvascular endothelial cells. Exp Ther Med 13(4):1225–1234. https://doi.org/10.3892/etm.2017.4095CrossRefPubMedPubMedCentral

27.

Li S, Pan X, Yang S, Ma A, Yin S, Dong Y, Pei H, Bi X, Li W (2019) LncRNA MALAT1 promotes oxidized low-density lipoprotein-induced autophagy in HUVECs by inhibiting the PI3K/AKT pathway. J Cell Biochem 120(3):4092–4101. https://doi.org/10.1002/jcb.27694CrossRefPubMed

28.

Yu Q, Xiang L, Chen Z, Liu X, Ou H, Zhou J, Yang D (2019) MALAT1 functions as a competing endogenous RNA to regulate SMAD5 expression by acting as a sponge for miR-142-3p in hepatocellular carcinoma. Cell Biosci 9:39. https://doi.org/10.1186/s13578-019-0299-6CrossRefPubMedPubMedCentral

29.

Jin C, Xiao L, Zhou Z, Zhu Y, Tian G, Ren S (2019) MiR-142-3p suppresses the proliferation, migration and invasion through inhibition of NR2F6 in lung adenocarcinoma. Hum Cell 32(4):437–446. https://doi.org/10.1007/s13577-019-00258-0CrossRefPubMed

30.

Qin B, Shu Y, Long L, Li H, Men X, Feng L, Yang H, Lu Z (2018) MicroRNA-142-3p Induces atherosclerosis-associated endothelial cell apoptosis by directly targeting rictor. Cell Physiol Biochem 47(4):1589–1603. https://doi.org/10.1159/000490932CrossRefPubMed

31.

Song B, Song WG, Li ZJ, Xu ZF, Wang XW, Wang CX, Liu J (2012) Effect of HMGB1 silencing on cell proliferation, invasion and apoptosis of MGC-803 gastric cancer cells. Cell Biochem Funct 30(1):11–17. https://doi.org/10.1002/cbf.1811CrossRefPubMed

32.

Liang L, Fu J, Wang S, Cen H, Zhang L, Mandukhail SR, Du L, Wu Q, Zhang P, Yu X (2020) MiR-142-3p enhances chemosensitivity of breast cancer cells and inhibits autophagy by targeting HMGB1. Acta pharmaceutica Sinica B 10(6):1036–1046. https://doi.org/10.1016/j.apsb.2019.11.009CrossRefPubMed

Titel: Long non-coding RNA MALAT1 affects intermittent hypoxia-induced endothelial injury by regulating miR-142-3p/HMGB1
verfasst von: Meng-Xue Chen
Li-Da Chen
Jian-Chai Huang
Ai-Ming Zeng
Jie-Feng Huang
Qi-Chang Lin
Publikationsdatum: 10.01.2022
Verlag: Springer International Publishing
Erschienen in: Sleep and Breathing / Ausgabe 4/2022
Print ISSN: 1520-9512
Elektronische ISSN: 1522-1709
DOI: https://doi.org/10.1007/s11325-021-02545-3

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Long non-coding RNA MALAT1 affects intermittent hypoxia-induced endothelial injury by regulating miR-142-3p/HMGB1