Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Long Noncoding RNA MHRT Protects Cardiomyocytes against H2O2-Induced Apoptosis

  • Zhang, Jianying (Department of Emergency, Maternity and Child Care Hospital) ;
  • Gao, Caihua (Department of Medical Services, Maternity and Child Care Hospital) ;
  • Meng, Meijuan (Department of Cardiology, Maternity and Child Care Hospital) ;
  • Tang, Hongxia (Department of Emergency, Maternity and Child Care Hospital)
  • Received : 2015.06.01
  • Accepted : 2015.07.13
  • Published : 2016.01.01
Download PDF
⟨ Previous Next ⟩

Abstract

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. The exploration of new biomarkers with high sensitivity and specificity for early diagnosis of AMI therefore becomes one of the primary task. In the current study, we aim to detect whether there is any heart specific long noncoding RNA (lncRNA) releasing into the circulation during AMI, and explore its function in the neonatal rat cardiac myocytes injury induced by $H_2O_2$. Our results revealed that the cardiac-specific lncRNA MHRT (Myosin Heavy Chain Associated RNA Transcripts) was significantly elevated in the blood from AMI patients compared with the healthy control ($^*p<0.05$). Using an in vitro neonatal rat cardiac myocytes injury model, we demonstrated that lncRNA MHRT was upregulated in the cardiac myocytes after treatment with hydrogen peroxide ($H_2O_2$) via real-time RT-PCR (qRT-PCR). Furthermore, we knockdowned the MHRT gene by siRNA to confirm its roles in the $H_2O_2$-induced cardiac cell apoptosis, and found that knockdown of MHRT led to significant more apoptotic cells than the non-target control ($^{**}p<0.01$), indicating that the lncRNA MHRT is a protective factor for cardiomyocyte and the plasma concentration of MHRT may serve as a biomarker for myocardial infarction diagnosis in humans AMI.

Keywords

References

  1. Batista, P. J. and Chang, H. Y. (2013) Long noncoding RNAs: cellular address codes in development and disease. Cell 152, 1298-1307. https://doi.org/10.1016/j.cell.2013.02.012
  2. Berg, K., Jynge, P., Bjerve, K., Skarra, S., Basu, S. and Wiseth, R. (2005) Oxidative stress and inflammatory response during and following coronary interventions for acute myocardial infarction. Free Radic. Res. 39, 629-636. https://doi.org/10.1080/10715760400028027
  3. Han, P., Li, W., Lin, C. H., Yang, J., Shang, C., Nurnberg, S. T., Jin, K. K., Xu, W., Lin, C. Y., Lin, C. J., Xiong, Y., Chien, H. C., Zhou, B., Ashley, E., Bernstein, D., Chen, P. S., Chen, H. S., Quertermous, T. and Chang, C. P. (2014) A long noncoding RNA protects the heart from pathological hypertrophy. Nature 514, 102-106. https://doi.org/10.1038/nature13596
  4. Jiang, X. and Ning, Q. (2015) The emerging roles of long noncoding RNAs in common cardiovascular diseases. Hypertens. Res. 38, 375-379. https://doi.org/10.1038/hr.2015.26
  5. Kanduri, C. (2015) Long noncoding RNAs: lessons from genomic imprinting. Biochim. Biophys. Acta [Epub ahed of print]
  6. Li, C., Fang, Z., Jiang, T., Zhang, Q., Liu, C., Zhang, C. and Xiang, Y. (2013) Serum microRNAs profile from genome-wide serves as a fingerprint for diagnosis of acute myocardial infarction and angina pectoris. BMC Med. Genomics 6, 16. https://doi.org/10.1186/1755-8794-6-16
  7. Mercer, T. R., Dinger, M. E. and Mattick, J. S. (2009) Long non-coding RNAs: insights into functions. Nat. Rev. Genet 10, 155-159. https://doi.org/10.1038/nrg2521
  8. Mercer, T. R. and Mattick, J. S. (2013) Structure and function of long noncoding RNAs in epigenetic regulation. Nat. Struct. Mol. Biol. 20, 300-307. https://doi.org/10.1038/nsmb.2480
  9. Ounzain, S., Crippa, S. and Pedrazzini, T. (2013) Small and long noncoding RNAs in cardiac homeostasis and regeneration. Biochim. Biophys. Acta 1833, 923-933. https://doi.org/10.1016/j.bbamcr.2012.08.010
  10. Ounzain, S., Pezzuto, I., Micheletti, R., Burdet, F., Sheta, R., Nemir, M., Gonzales, C., Sarre, A., Alexanian, M., Blow, M. J., May, D., Johnson, R., Dauvillier, J., Pennacchio, L. A. and Pedrazzini, T. (2014) Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease. J. Mol. Cell. Cardiol. 76, 55-70. https://doi.org/10.1016/j.yjmcc.2014.08.009
  11. Pedrazzini, T. (2015) [In the heart of noncoding RNA: a long way to go]. Med. Sci. 31, 261-267.
  12. Thygesen, K., Alpert, J. S., White, H. D. and Joint, E. S. C. A. A. H. A. W. H. F. T. F. f. t. R. o. M. I. (2007) Universal definition of myocardial infarction. J. Am. Coll. Cardiol. 50, 2173-2195. https://doi.org/10.1016/j.jacc.2007.09.011
  13. Uchida, S. and Dimmeler, S. (2015) Long noncoding RNAs in cardiovascular diseases. Circ. Res. 116, 737-750. https://doi.org/10.1161/CIRCRESAHA.116.302521
  14. Vausort, M., Wagner, D. R. and Devaux, Y. (2014) Long noncoding RNAs in patients with acute myocardial infarction. Circ. Res. 115, 668-677. https://doi.org/10.1161/CIRCRESAHA.115.303836
  15. Wang, J., Jia, Z., Zhang, C., Sun, M., Wang, W., Chen, P., Ma, K., Zhang, Y., Li, X. and Zhou, C. (2014) miR-499 protects cardiomyocytes from$H_{2}O_{2}$-induced apoptosis via its effects on Pdcd4 and Pacs2. RNA Biol. 11, 339-350. https://doi.org/10.4161/rna.28300
  16. Wu, C. and Arora, P. (2015) Long noncoding Mhrt RNA: molecular crowbar unravel insights into heart failure treatment. Circ. Cardiovasc. Genet. 8, 213-215. https://doi.org/10.1161/CIRCGENETICS.115.001019
  17. Xu, J., Zhao, J., Evan, G., Xiao, C., Cheng, Y. and Xiao, J. (2012) Circulating microRNAs: novel biomarkers for cardiovascular diseases. J. Mol. Med. 90, 865-875. https://doi.org/10.1007/s00109-011-0840-5
  18. Yao, Y., Du, J., Cao, X., Wang, Y., Huang, Y., Hu, S. and Zheng, Z. (2014) Plasma levels of microRNA-499 provide an early indication of perioperative myocardial infarction in coronary artery bypass graft patients. PLoS One 9, e104618. https://doi.org/10.1371/journal.pone.0104618

Cited by

  1. Regulatory non-coding RNAs in acute myocardial infarction vol.21, pp.5, 2017, https://doi.org/10.1111/jcmm.13032
  2. Emerging roles and mechanisms of long noncoding RNAs in atherosclerosis vol.228, 2017, https://doi.org/10.1016/j.ijcard.2016.11.182
  3. Knockdown of Long Non-Coding RNA-ZFAS1 Protects Cardiomyocytes Against Acute Myocardial Infarction Via Anti-Apoptosis by Regulating miR-150/CRP vol.118, pp.10, 2017, https://doi.org/10.1002/jcb.25979
  4. Long noncoding RNAs (LncRNAs) — The dawning of a new treatment for cardiac hypertrophy and heart failure vol.1863, pp.8, 2017, https://doi.org/10.1016/j.bbadis.2017.02.024
  5. Circulating long non-coding RNAs NRON and MHRT as novel predictive biomarkers of heart failure vol.21, pp.9, 2017, https://doi.org/10.1111/jcmm.13101
  6. Noncoding RNAs and Their Potential Therapeutic Applications in Tissue Engineering vol.3, pp.1, 2017, https://doi.org/10.1016/J.ENG.2017.01.005
  7. Circulating Noncoding RNAs as Biomarkers of Cardiovascular Disease and Injury vol.120, pp.2, 2017, https://doi.org/10.1161/CIRCRESAHA.116.308434
  8. , their expression levels in peripheral blood mononuclear cells in patients with essential hypertension and their relation to heart hypertrophy vol.45, pp.11, 2018, https://doi.org/10.1111/1440-1681.12997
  9. Redox Regulation and Noncoding RNAs vol.29, pp.9, 2018, https://doi.org/10.1089/ars.2017.7276
  10. Non-coding RNAs as therapeutic targets for preventing myocardial ischemia-reperfusion injury vol.22, pp.3, 2018, https://doi.org/10.1080/14728222.2018.1439015
  11. Diagnostic Value of the lncRNA NEAT1 in Peripheral Blood Mononuclear Cells of Patients with Sepsis vol.2017, pp.None, 2017, https://doi.org/10.1155/2017/7962836
  12. THE PARTICIPATION OF LONG NONCODING RNAs IN CARDIAC HYPERTROPHY FORMATION DURING LONGLASTING PHYSICAL EXERCISE vol.2017, pp.4, 2016, https://doi.org/10.29254/2077-4214-2017-4-3-141-38-43
  13. Diagnostic potential of circulating LncRNAs in human cardiovascular disease: a meta-analysis vol.38, pp.6, 2016, https://doi.org/10.1042/bsr20181610
  14. Evolutionary Patterns of Non-Coding RNA in Cardiovascular Biology vol.5, pp.1, 2016, https://doi.org/10.3390/ncrna5010015
  15. Novel Findings and Therapeutic Targets on Cardioprotection of Ischemia/ Reperfusion Injury in STEMI vol.25, pp.35, 2019, https://doi.org/10.2174/1381612825666191105103417
  16. The roles of long noncoding RNAs in myocardial pathophysiology vol.39, pp.11, 2019, https://doi.org/10.1042/bsr20190966
  17. Myosin Heavy Chain-Associated RNA Transcripts Promotes Gastric Cancer Progression Through the miR-4529-5p/ROCK2 Axis vol.64, pp.12, 2016, https://doi.org/10.1007/s10620-019-05708-1
  18. Noncoding RNAs as Biomarkers for Acute Coronary Syndrome vol.2020, pp.None, 2020, https://doi.org/10.1155/2020/3298696
  19. Preparation and appraisal of self-assembled valsartan-loaded amalgamated Pluronic F127/Tween 80 polymeric micelles: Boosted cardioprotection via regulation of Mhrt/Nrf2 and Trx1 pathways in cisplatin- vol.28, pp.3, 2020, https://doi.org/10.1080/1061186x.2019.1650053
  20. Oncostatin M upregulates Livin to promote keratinocyte proliferation and survival via ERK and STAT3 signalling pathways vol.105, pp.7, 2016, https://doi.org/10.1113/ep088584
  21. The functions of LncRNA in the heart vol.168, pp.None, 2016, https://doi.org/10.1016/j.diabres.2020.108249
  22. LncRNA MHRT Promotes Cardiac Fibrosis via miR-3185 Pathway Following Myocardial Infarction vol.62, pp.4, 2016, https://doi.org/10.1536/ihj.20-298
  23. LncRNA TTTY15 knockdown alleviates H2O2-stimulated myocardial cell injury by regulating the miR-98-5p/CRP pathway vol.476, pp.1, 2016, https://doi.org/10.1007/s11010-020-03887-4
  24. Long Non-Coding RNAs (lncRNAs) in Cardiovascular Disease Complication of Type 2 Diabetes vol.11, pp.1, 2021, https://doi.org/10.3390/diagnostics11010145
  25. Role of N6-Methyladenosine RNA Modification in Cardiovascular Disease vol.8, pp.None, 2016, https://doi.org/10.3389/fcvm.2021.659628
  26. Role of long non‐coding RNAs in adipogenesis: State of the art and implications in obesity and obesity‐associated diseases vol.22, pp.7, 2016, https://doi.org/10.1111/obr.13203
  27. Novel Biomarkers in Heart Failure: New Insight in Pathophysiology and Clinical Perspective vol.10, pp.13, 2016, https://doi.org/10.3390/jcm10132771
  28. MHRT expression during remote ischemic preconditioning in patients with coronary artery disease vol.37, pp.4, 2021, https://doi.org/10.7124/bc.000a59
  29. Inhibition of the lncRNA DANCR attenuates cardiomyocyte injury induced by oxygen-glucose deprivation via the miR-19a-3p/MAPK1 axis vol.53, pp.10, 2016, https://doi.org/10.1093/abbs/gmab110
  30. Long Non-Coding RNAs in Cardiovascular Diseases: Potential Function as Biomarkers and Therapeutic Targets of Exercise Training vol.7, pp.4, 2016, https://doi.org/10.3390/ncrna7040065