Kardiyovasküler Hastalıklarda Uzun Kodlamayan RNA’lar ve Sirküler RNA’ların Önemi

Yıl 2019, , 115 - 125, 30.12.2019

Hilal Şentürk Evrim Komurcu-bayrak

https://doi.org/10.26650/JARHS2019-638138

Öz

Kardiyovasküler hastalıklar (KVH'lar), mortalite ve morbiditenin en önemli nedeni olup çoğunlukla yetişkinlerde gözlenmektedir. KVH’ların altında yatan ana mekanizma, fibröz plakların oluşumu, düz kas hücrelerinin çoğalması ve enflamatuvar hücrelerin göçü ile meydana gelen karmaşık bir patoloji olan aterosklerozdur. Son çalışmalar, uzun kodlamayan RNA'lar (lncRNA) ve dairesel RNA'lar (circRNA) gibi protein kodlamayan RNA'ların, ateroskleroz dahil tüm KVH’ların epigenetiğinde önemli düzenleyici rollere sahip olduğunu göstermektedir. Bu derlemede, lncRNA'ların ve circRNA'ların fonksiyonel aktiviteleri ve bunların ateroskleroz ve KVH’larla olan ilişkileri özetlenmektedir.

Anahtar Kelimeler

Kardiyovasküler hastalıklar, uzun kodlamayan RNA, sirküler RNA

Destekleyen Kurum

İstanbul Üniversitesi Bilimsel Araştırma Projeleri Birimi

Proje Numarası

TYL-2017-27636

The Importance of Long Noncoding RNAs in Cardiovascular Diseases

Öz

Cardiovascular diseases (CVDs) are a leading cause of mortality and morbidity and mostly affect adults. The main underlying mechanism of CVDs is atherosclerosis and this complex pathology is caused by the formation of fibrous plaques, the proliferation of smooth muscle cells and the migration of inflammatory cells. Recent studies suggest that noncoding RNAs such as long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have critical regulatory roles in the epigenetics of all CVDs including atherosclerosis. This review summarizes the functional roles of lncRNAs and circRNAs and their relationships with atherosclerosis and CVDs. 

Anahtar Kelimeler

Cardiovascular diseases, long noncoding RNA, circular RNA

Proje Numarası

TYL-2017-27636

Kaynakça

• 1. Karaarslan Z.Ö., Serin M.S. (2016): Hastalıkların tanı ve tedavi stratejilerinde miRNA ve diğer non-proteincoding RNA’lar. Mersin Univ Saglık Bilim Derg,(9)3.
• 2. Zhang F, Zhang R, Zhang X, Wu Y, Li X, Zhang S, Hou W, Ding Y, Tian J, Sun L, Kong X. (2018): Comprehensive analysis of circRNA expression pattern and circRNAmiRNA-mRNA network in the pathogenesis of atherosclerosis in rabbits.Aging (Albany NY), 10(9):2266-2283.
• 3. Klattenhoff CA, Scheuermann JC, Surface LE, Bradley RK, Fields PA, Steinhauser ML, ve ark. (2013): Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell, 152(3): 570583.
• 4. Kumarswamy R, Bauters C, Volkmann I, Maury F, Fetisch J, Holzmann A, ve ark. (2014):Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure. Circ Res, 114(10): 1569-1575.
• 5. Archer K, Broskova Z, Bayoumi AS, Teoh JP, Davila A, Tang Y, ve ark. (2015): Long Non-Coding RNAs as Master Regulators in Cardiovascular Diseases. Int J Mol Sci, 16(10): 23651-23667.
• 6. Wang W, Wang Y, Piao H, Li B, Huang M, Zhu Z, Li D, Wang T, Xu R, Liu K. (2019): Circular RNAs as potential biomarkers and therapeutics for cardiovascular disease. PeerJ, 7:e6831.
• 7. Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, Barrette TR, et al. (2015): The landscape of long noncoding RNAs in the human transcriptome. Nat Genet., 47:199–208.
• 8. Scheuermann JC, Boyer LA. (2013): Getting to the heart of the matter: long non-coding RNAs in cardiac development and disease. EMBO J., 32(13): 1805-1816.
• 9. Bayoğlu B, Cengiz M. (2017): Kalp ve Damar Hastalıklarında Uzun Kodlanmayan RNA Transkriptlerinin Rolleri. Bezmialem Science, 5: 74-79.
• 10. Lee JT. (2012): Epigenetic regulation by long noncoding RNAs. Science, 338(6113): 1435-1439.
• 11. Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, ve ark. (2007): RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science, 316(5830): 1484-1488.
• 12. Sana J, Faltejskova P, Svoboda M, Slaby O. (2012) Novel classes of non-coding RNAs and cancer. J Transl Med., 10: 103.
• 13. Tian D, Sun S, Lee JT. (2010): The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell.,143(3): 390-403.
• 14. Hung T, Wang Y, Lin MF, Koegel AK, Kotake Y, Grant GD, ve ark. (2011): Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet, 43(7): 621-629.
• 15. Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, Watt AT, ve ark. (2010): The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell, 39(6): 925-938.
• 16. Wang KC, Chang HY. (2011): Molecular mechanisms of long noncoding RNAs. Mol Cell, 43(6): 904-914.
• 17. Bayoumi AS, Aonuma T, Teoh JP, Tang YL, Kim IM. (2018): Circular noncoding RNAs as potential therapies and circulating biomarkers for cardiovascular diseases. Acta Pharmacol Sin., 39(7):1100-1109.
• 18. Schwartz SM. (1997): Smooth muscle migration in atherosclerosis and restenosis. J Clin Invest, 100(11 Suppl): S87-89.
• 19. Motterle A, Pu X, Wood H, Xiao Q, Gor S, Ng FL, ve ark.( 2012): Functional analyses of coronary artery disease associated variation on chromosome 9p21 in vascular smooth muscle cells. Hum Mol Genet, 21(18): 4021-4029.
• 20. Holdt LM, Teupser D. (2012): Recent studies of the human chromosome 9p21 locus, which is associated with atherosclerosis in human populations. Arterioscler Thromb Vasc Biol, 32(2): 196-206. 21. Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, ve ark. (2007): Genomewide association analysis of coronary artery disease. N Engl J Med, 357(5): 443-453.
• 22. Holdt LM, Hoffmann S, Sass K, Langenberger D, Scholz M, Krohn K, ve ark. (2013): Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks. PLoS Genet, 9(7): e1003588.
• 23. Holdt LM, Beutner F, Scholz M, Gielen S, Gabel G, Bergert H, ve ark. (2010): ANRIL expression is associated with atherosclerosis risk at chromosome 9p21. Arterioscler Thromb Vasc Biol, 30(3): 620-627.
• 24. Li H, Zhu H, Ge J. (2016): Long Noncoding RNA: Recent Updates in Atherosclerosis. Int J Biol Sci, 12(7): 898-910.
• 25. Nabel EG, Braunwald E. (2012): A tale of coronary artery disease and myocardial infarction. N Engl J Med, 366(1): 54-63.
• 26. Michalik KM, You X, Manavski Y, Doddaballapur A, Zornig M, Braun T, ve ark. (2014): Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res, 114(9): 1389-1397.
• 27. Hu YW, Yang JY, Ma X, Chen ZP, Hu YR, Zhao JY, ve ark. (2014): A lincRNA-DYNLRB2-2/GPR119/GLP-1R/ ABCA1-dependent signal transduction pathway is essential for the regulation of cholesterol homeostasis. J Lipid Res, 55(4): 681-697.
• 28. Hu YW, Zhao JY, Li SF, Huang JL, Qiu YR, Ma X, ve ark. (2015): RP5-833A20.1/miR-382-5p/NFIAdependent signal transduction pathway contributes to the regulation of cholesterol homeostasis and inflammatory reaction. Arterioscler Thromb Vasc Biol, 35(1): 87-101.
• 29. Şengül C. (2006): Genç Yaşta Miyokard Enfarktüsü Geçiren Hastalarda Klasik Ve Psikososyal Risk Faktörlerinin Karşılaştırmalı Olarak İncelenmesi. Kardiyoloji Uzmanlık Tezi, İstanbul.
• 30. Vausort M, Wagner DR, Devaux Y. (2014): Long noncoding RNAs in patients with acute myocardial infarction. Circ Res, 115(7): 668-677.
• 31. Lu Y, Meng X, Wang L, Wang X. (2018): Analysis of long non-coding RNA expression profiles identifies functional lncRNAs associated with the progression of acute coronary syndromes. Exp Ther Med, 15(2): 1376-1384.
• 32. Wang K., Liu C.Y., Zhou L.Y., Wang J.X., Wang M. ve ark. (2015): APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p. Nat Commun, 10;6:6779.
• 33. White HD, ed Unstable Angina: Ischemic Syndromes. 3 ed. Philadelphia: Lippincott Williams & Wilkins; 2007. Topol EJ, ed. Textbook of cardiovascular medicine.
• 34. Cai Y, Yang Y, Chen X, Wu G, Zhang X, Liu Y, ve ark. (2016): Circulating ‘lncRNA OTTHUMT00000387022’ from monocytes as a novel biomarker for coronary artery disease. Cardiovasc Res, 112(3): 714-724.
• 35. Holdt LM, Stahringer A, Sass K, Pichler G, Kulak NA, ve ark. (2016): Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nat Commun., 7:12429.
• 36. Holdt LM, Teupser D. (2018): Long Noncoding RNA ANRIL: Lnc-ing Genetic Variation at the Chromosome 9p21 Locus to Molecular Mechanisms of Atherosclerosis. Front Cardiovasc Med., 6;5:145.
• 37. Rankin CR, Lokhandwala ZA, Huang R, Pekow J, Pothoulakis C, Padua D. (2019): Linear and circular CDKN2B-AS1 expression is associated with Inflammatory Bowel Disease and participates in intestinal barrier formation. Life Sci., 231:116571.
• 38. Salgado-Somoza A, Zhang L, Vausort M, Devaux Y. (2017): The circular RNA MICRA for risk stratification after myocardial infarction. International Journal of Cardiology, Heart andVasculature 17:33–36.
• 39. Yang Y, Cai Y, Wu G, Chen X, Liu Y, Wang X, ve ark. (2015): Plasma long non-coding RNA, CoroMarker, a novel biomarker for diagnosis of coronary artery disease. Clin Sci (Lond), 129(8): 675-685.