Top

Published in:

20-06-2022 | Septicemia

LncRNA MALAT1 Regulates USP22 Expression Through EZH2-Mediated H3K27me3 Modification to Accentuate Sepsis-Induced Myocardial Dysfunction

Authors: Hong Xu, Wei Ye, Baochang Shi

Published in: Cardiovascular Toxicology | Issue 9/2022

Abstract

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), has been confirmed to recruit enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) to regulate cardiomyocyte apoptosis in diabetic cardiomyopathy. However, whether the similar regulatory axis exists in sepsis-induced myocardial dysfunction (SIMD) has not been clearly established. The current study sought to define the mechanism governing MALAT1-mediated EZH2 in SIMD. MALAT1 was significantly upregulated in lipopolysaccharide-induced cardiomyocytes. Depletion of MALAT1 by caudal vein injection of small interfering RNA targeting MALAT1 alleviated myocardial injury in SIMD rats, restored cardiac function, reduced oxidative stress production and fibrosis, and inhibited inflammatory factors and apoptosis in myocardial tissues. Moreover, MALAT1 bound to EZH2 and promoted EZH2 activity in the nucleus of cardiomyocytes. EZH2 repressed ubiquitin-specific peptidase 22 (USP22) expression through H3K27me3 modification. EZH2 elevation aggravated the cardiac injury in SIMD rats, while USP22 upregulation inhibited the effect of EZH2, which reduced the cardiac injury in SIMD rats. Taken together, MALAT1 decreased USP22 expression by interacting with EZH2, thereby worsening SIMD, highlighting an attractive therapeutic strategy for SIMD.

Deutschman, C. S., & Tracey, K. J. (2014). Sepsis: Current dogma and new perspectives. Immunity, 40(4), 463–475. https://doi.org/10.1016/j.immuni.2014.04.001CrossRefPubMed

Kumar, S., Tripathy, S., Jyoti, A., & Singh, S. G. (2019). Recent advances in biosensors for diagnosis and detection of sepsis: A comprehensive review. Biosensors & Bioelectronics, 124–125, 205–215. https://doi.org/10.1016/j.bios.2018.10.034CrossRef

Hollenberg, S. M., & Singer, M. (2021). Pathophysiology of sepsis-induced cardiomyopathy. Nature Reviews Cardiology, 18(6), 424–434. https://doi.org/10.1038/s41569-020-00492-2CrossRefPubMed

Walley, K. R. (2018). Sepsis-induced myocardial dysfunction. Current Opinion in Critical Care, 24(4), 292–299. https://doi.org/10.1097/MCC.0000000000000507CrossRefPubMed

Lin, Y., Xu, Y., & Zhang, Z. (2020). Sepsis-Induced Myocardial Dysfunction (SIMD): The pathophysiological mechanisms and therapeutic strategies targeting mitochondria. Inflammation, 43(4), 1184–1200. https://doi.org/10.1007/s10753-020-01233-wCrossRefPubMed

Boon, R. A., Jae, N., Holdt, L., & Dimmeler, S. (2016). Long noncoding RNAs: From clinical genetics to therapeutic targets? Journal of the American College of Cardiology, 67(10), 1214–1226. https://doi.org/10.1016/j.jacc.2015.12.051CrossRefPubMed

Zhang, T. N., Goodwin, J. E., Liu, B., Li, D., Wen, R., Yang, N., Xia, J., Zhou, H., Zhang, T., Song, W. L., & Liu, C. F. (2019). Characterization of long noncoding RNA and mRNA profiles in sepsis-induced myocardial depression. Molecular Therapy—Nucleic Acids, 17, 852–866. https://doi.org/10.1016/j.omtn.2019.07.020CrossRefPubMedPubMedCentral

Hu, H., Wu, J., Yu, X., Zhou, J., Yu, H., & Ma, L. (2019). Long non-coding RNA MALAT1 enhances the apoptosis of cardiomyocytes through autophagy inhibition by regulating TSC2-mTOR signaling. Biological Research, 52(1), 58. https://doi.org/10.1186/s40659-019-0265-0CrossRefPubMedPubMedCentral

Wang, J., & Wang, G. G. (2020). No easy way out for EZH2: Its pleiotropic, noncanonical effects on gene regulation and cellular function. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms21249501CrossRefPubMedPubMedCentral

10.

Shyni, G. L., Renjitha, J., Sasidhar Somappa, & Raghu, K. G. (2021). Zerumin A attenuates the inflammatory responses in LPS-stimulated H9c2 cardiomyoblasts. Journal of Biochemical and Molecular Toxicology, 35(6), 1–11. https://doi.org/10.1002/jbt.22777CrossRefPubMed

11.

Wu, B., Ni, H., Li, J., Zhuang, X., Zhang, J., Qi, Z., Chen, Q., Wen, Z., Shi, H., Luo, X., & Jin, B. (2017). The impact of circulating mitochondrial DNA on cardiomyocyte apoptosis and myocardial injury after TLR4 activation in experimental autoimmune myocarditis. Cellular Physiology and Biochemistry, 42(2), 713–728. https://doi.org/10.1159/000477889CrossRefPubMed

12.

Zhang, Y., Huang, H., Liu, W., Liu, S., Wang, X. Y., Diao, Z. L., Zhang, A. H., Guo, W., Han, X., Dong, X., & Katilov, O. (2021). Endothelial progenitor cells-derived exosomal microRNA-21-5p alleviates sepsis-induced acute kidney injury by inhibiting RUNX1 expression. Cell Death & Disease, 12(4), 335. https://doi.org/10.1038/s41419-021-03578-yCrossRef

13.

L’Heureux, M., Sternberg, M., Brath, L., Turlington, J., & Kashiouris, M. G. (2020). Sepsis-induced cardiomyopathy: A comprehensive review. Current Cardiology Reports, 22(5), 35. https://doi.org/10.1007/s11886-020-01277-2CrossRefPubMedPubMedCentral

14.

Lv, X., & Wang, H. (2016). Pathophysiology of sepsis-induced myocardial dysfunction. Military Medical Research, 3, 30. https://doi.org/10.1186/s40779-016-0099-9CrossRefPubMedPubMedCentral

15.

Li, C., Liu, Y., Qin, J., Liu, Y., Ma, L., Zhang, S., Wang, J., & Wang, S. (2021). Profiles of differentially expressed long noncoding RNAs and messenger RNAs in the myocardium of septic mice. Annals of Translational Medicine, 9(3), 199. https://doi.org/10.21037/atm-20-3830CrossRefPubMedPubMedCentral

16.

Hu, H., Wu, J., Li, D., Zhou, J., Yu, H., & Ma, L. (2018). Knockdown of lncRNA MALAT1 attenuates acute myocardial infarction through miR-320-Pten axis. Biomedicine & Pharmacotherapy, 106, 738–746. https://doi.org/10.1016/j.biopha.2018.06.122CrossRef

17.

Cui, N., Liang, Y., Wang, J., Liu, B., Wei, B., & Zhao, Y. (2021). Minocycline attenuates oxidative and inflammatory injury in a intestinal perforation induced septic lung injury model via down-regulating lncRNA MALAT1 expression. International Immunopharmacology, 100, 108115. https://doi.org/10.1016/j.intimp.2021.108115CrossRefPubMed

18.

Jia, P., Wu, N., Jia, D., & Sun, Y. (2019). Downregulation of MALAT1 alleviates saturated fatty acid-induced myocardial inflammatory injury via the miR-26a/HMGB1/TLR4/NF-kappaB axis. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 12, 655–665. https://doi.org/10.2147/DMSO.S203151CrossRef

19.

Jing, H., Wang, C., Zhao, L., Cheng, J., Qin, P., & Lin, H. (2021). Propofol protects cardiomyocytes from hypoxia/reoxygenation injury via regulating MALAT1/miR-206/ATG3 axis. Journal of Biochemical and Molecular Toxicology, 35(10), e22880. https://doi.org/10.1002/jbt.22880CrossRefPubMed

20.

Liu, L., Yan, L. N., & Sui, Z. (2021). MicroRNA-150 affects endoplasmic reticulum stress via MALAT1-miR-150 axis-mediated NF-kappaB pathway in LPS-challenged HUVECs and septic mice. Life Sciences, 265, 118744. https://doi.org/10.1016/j.lfs.2020.118744CrossRefPubMed

21.

Han, L., & Yang, L. (2021). Multidimensional mechanistic spectrum of long non-coding RNAs in heart development and disease. Front Cardiovasc Med, 8, 728746. https://doi.org/10.3389/fcvm.2021.728746CrossRefPubMedPubMedCentral

22.

Muthumani, M., & Prabu, S. M. (2014). Silibinin potentially attenuates arsenic-induced oxidative stress mediated cardiotoxicity and dyslipidemia in rats. Cardiovascular Toxicology, 14(1), 83–97. https://doi.org/10.1007/s12012-013-9227-xCrossRefPubMed

23.

Qu, D., Sun, W. W., Li, L., Ma, L., Sun, L., Jin, X., Li, T., Hou, W., & Wang, J. H. (2019). Long noncoding RNA MALAT1 releases epigenetic silencing of HIV-1 replication by displacing the polycomb repressive complex 2 from binding to the LTR promoter. Nucleic Acids Research, 47(6), 3013–3027. https://doi.org/10.1093/nar/gkz117CrossRefPubMedPubMedCentral

24.

Wang, C., Liu, G., Yang, H., Guo, S., Wang, H., Dong, Z., Li, X., Bai, Y., & Cheng, Y. (2021). MALAT1-mediated recruitment of the histone methyltransferase EZH2 to the microRNA-22 promoter leads to cardiomyocyte apoptosis in diabetic cardiomyopathy. Science of the Total Environment, 766, 142191. https://doi.org/10.1016/j.scitotenv.2020.142191CrossRefPubMed

25.

Yong, H., Wu, G., Chen, J., Liu, X., Bai, Y., Tang, N., Liu, L., & Wei, J. (2020). lncRNA MALAT1 accelerates skeletal muscle cell apoptosis and inflammatory response in sepsis by decreasing BRCA1 expression by recruiting EZH2. Mol Ther Nucleic Acids, 21, 1120–1121. https://doi.org/10.1016/j.omtn.2020.07.033CrossRefPubMedPubMedCentral

26.

Yu, Z., Rayile, A., Zhang, X., Li, Y., & Zhao, Q. (2017). Ulinastatin protects against lipopolysaccharide-induced cardiac microvascular endothelial cell dysfunction via downregulation of lncRNA MALAT1 and EZH2 in sepsis. International Journal of Molecular Medicine, 39(5), 1269–1276. https://doi.org/10.3892/ijmm.2017.2920CrossRefPubMed

27.

Cai, L. J., Tu, L., Huang, X. M., Huang, J., Qiu, N., Xie, G. H., Liao, J. X., Du, W., Zhang, Y. Y., & Tian, J. Y. (2020). LncRNA MALAT1 facilitates inflammasome activation via epigenetic suppression of Nrf2 in Parkinson’s disease. Molecular Brain, 13(1), 130. https://doi.org/10.1186/s13041-020-00656-8CrossRefPubMedPubMedCentral

28.

Liang, H., Huang, Q., Liao, M. J., Xu, F., Zhang, T., He, J., Zhang, L., & Liu, H. Z. (2019). EZH2 plays a crucial role in ischemia/reperfusion-induced acute kidney injury by regulating p38 signaling. Inflammation Research, 68(4), 325–336. https://doi.org/10.1007/s00011-019-01221-3CrossRefPubMed

29.

Liu, H., Chen, Z., Weng, X., Chen, H., Du, Y., Diao, C., Liu, X., & Wang, L. (2020). Enhancer of zeste homolog 2 modulates oxidative stress-mediated pyroptosis in vitro and in a mouse kidney ischemia-reperfusion injury model. The FASEB Journal, 34(1), 835–852. https://doi.org/10.1096/fj.201901816RCrossRefPubMed

30.

Peng, Y., Zhao, J. L., Peng, Z. Y., Xu, W. F., & Yu, G. L. (2020). Exosomal miR-25-3p from mesenchymal stem cells alleviates myocardial infarction by targeting pro-apoptotic proteins and EZH2. Cell Death & Disease, 11(5), 317. https://doi.org/10.1038/s41419-020-2545-6CrossRef

31.

Melo-Cardenas, J., Zhang, Y., Zhang, D. D., & Fang, D. (2016). Ubiquitin-specific peptidase 22 functions and its involvement in disease. Oncotarget, 7(28), 44848–44856. https://doi.org/10.18632/oncotarget.8602CrossRefPubMedPubMedCentral

32.

Ma, S., Sun, L., Wu, W., Wu, J., Sun, Z., & Ren, J. (2020). USP22 protects against myocardial ischemia-reperfusion injury via the SIRT1-p53/SLC7A11-dependent inhibition of ferroptosis-induced cardiomyocyte death. Frontiers in Physiology, 11, 551318. https://doi.org/10.3389/fphys.2020.551318CrossRefPubMedPubMedCentral

Title: LncRNA MALAT1 Regulates USP22 Expression Through EZH2-Mediated H3K27me3 Modification to Accentuate Sepsis-Induced Myocardial Dysfunction
Authors: Hong Xu
Wei Ye
Baochang Shi
Publication date: 20-06-2022
Publisher: Springer US
Keywords: Septicemia
Septicemia
Published in: Cardiovascular Toxicology / Issue 9/2022
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-022-09758-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

LncRNA MALAT1 Regulates USP22 Expression Through EZH2-Mediated H3K27me3 Modification to Accentuate Sepsis-Induced Myocardial Dysfunction

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 9/2022

An Improved Monkey Model of Myocardial Ischemic Infarction for Cardiovascular Drug Development

Salvianolic Acid B Alleviates Myocardial Ischemia Injury by Suppressing NLRP3 Inflammasome Activation via SIRT1-AMPK-PGC-1α Signaling Pathway

Cardiac Remodelling Following Cancer Therapy: A Review

l-Carnitine Mitigates Trazadone Induced Rat Cardiotoxicity Mediated via Modulation of Autophagy and Oxidative Stress

Maternal Ethanol Exposure-Induced Cardiac Fibrosis is Associated with Changes in TGF-β and SIRT1/FOXO3a Signaling in Male Rat Offspring: A Three-Month Follow-up Study

QTc Prolongation in Poison Center Exposures to CredibleMeds List of Substances with “Known Risk of Torsades de Pointes”