Advertisement

Diverse roles of noncoding RNAs in vascular calcification

  • Young-Kook KimEmail author
  • Hyun KookEmail author
Review

Abstract

Vascular calcification occurs when calcium phosphate crystals are abnormally deposited in the vessel walls, thus hardening and narrowing the arteries. This condition is commonly observed in patients with diseases such as atherosclerosis, chronic kidney disease, diabetes, and cardiovascular diseases. Despite many studies being conducted, the molecular mechanism involved in vascular calcification is unknown. From recent studies, it is clear that several types of noncoding RNAs are involved in human diseases. It has also been shown that the noncoding RNAs, including microRNAs, long noncoding RNAs, and circular RNAs, are involved in the progression of vascular calcification. With the development of therapeutic approaches based on the manipulation of noncoding RNAs, it is speculated that the modulation of these molecules could be another strategy to treat vascular calcification in the future. In this review, we summarize the roles of various noncoding RNAs in vascular calcification and the technologies to modulate the noncoding RNAs for therapeutic purpose.

Keywords

Vascular calcification microRNA Long noncoding RNA Circular RNA 

Notes

Acknowledgements

This study was financially supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2018R1A2B6001104 and NRF-2018R1A2B3001503).

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

References

  1. Bartel DP (2018) Metazoan MicroRNAs. Cell 173:20–51CrossRefGoogle Scholar
  2. Baumann V, Winkler J (2014) miRNA-based therapies: strategies and delivery platforms for oligonucleotide and non-oligonucleotide agents. Future Med Chem 6:1967–1984CrossRefGoogle Scholar
  3. Boettcher M, Mcmanus MT (2015) Choosing the Right Tool for the Job: RNAi, TALEN, or CRISPR. Mol Cell 58:575–585CrossRefGoogle Scholar
  4. Boyce BF, Xing L (2007) Biology of RANK, RANKL, and osteoprotegerin. Arthr Res Ther 9(Suppl 1):S1CrossRefGoogle Scholar
  5. Carrion K, Dyo J, Patel V, Sasik R, Mohamed SA, Hardiman G, Nigam V (2014) The long non-coding HOTAIR is modulated by cyclic stretch and WNT/beta-CATENIN in human aortic valve cells and is a novel repressor of calcification genes. PLoS ONE 9:e96577CrossRefGoogle Scholar
  6. Cerritelli SM, Frolova EG, Feng C, Grinberg A, Love PE, Crouch RJ (2003) Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice. Mol Cell 11:807–815CrossRefGoogle Scholar
  7. Chakraborty C, Sharma AR, Sharma G, Doss CGP, Lee SS (2017) Therapeutic miRNA and siRNA: moving from bench to clinic as next generation medicine. Mol Ther Nucleic Acids 8:132–143CrossRefGoogle Scholar
  8. Chen J, Wang J, Jiang Y, Gu W, Ni B, Sun H, Gu W, Chen L, Shao Y (2018) Identification of circular RNAs in human aortic valves. Gene 642:135–144CrossRefGoogle Scholar
  9. Choe N, Kwon DH, Shin S, Kim YS, Kim YK, Kim J, Ahn Y, Eom GH, Kook H (2017) The microRNA miR-124 inhibits vascular smooth muscle cell proliferation by targeting S100 calcium-binding protein A4 (S100A4). FEBS Lett 591:1041–1052CrossRefGoogle Scholar
  10. Cui RR, Li SJ, Liu LJ, Yi L, Liang QH, Zhu X, Liu GY, Liu Y, Wu SS, Liao XB, Yuan LQ, Mao DA, Liao EY (2012) MicroRNA-204 regulates vascular smooth muscle cell calcification in vitro and in vivo. Cardiovasc Res 96:320–329CrossRefGoogle Scholar
  11. Disteche CM, Berletch JB (2015) X-chromosome inactivation and escape. J Genet 94:591–599CrossRefGoogle Scholar
  12. Du Y, Gao C, Liu Z, Wang L, Liu B, He F, Zhang T, Wang Y, Wang X, Xu M, Luo GZ, Zhu Y, Xu Q, Wang X, Kong W (2012) Upregulation of a disintegrin and metalloproteinase with thrombospondin motifs-7 by miR-29 repression mediates vascular smooth muscle calcification. Arterioscler Thromb Vasc Biol 32:2580–2588CrossRefGoogle Scholar
  13. Duarte WR, Shibata T, Takenaga K, Takahashi E, Kubota K, Ohya K, Ishikawa I, Yamauchi M, Kasugai S (2003) S100A4: a novel negative regulator of mineralization and osteoblast differentiation. J Bone Miner Res 18:493–501CrossRefGoogle Scholar
  14. Fatica A, Bozzoni I (2014) Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 15:7–21CrossRefGoogle Scholar
  15. Frankish A, Diekhans M, Ferreira AM, Johnson R, Jungreis I, Loveland J, Mudge JM, Sisu C, Wright J, Armstrong J, Barnes I, Berry A, Bignell A, Sala SC, Chrast J, Cunningham F, Di Domenico T, Donaldson S, Fiddes IT, Giron CG, Gonzalez JM, Grego T, Hardy M, Hourlier T, Hunt T, Izuogu OG, Lagarde J, Martin FJ, Martinez L, Mohanan S, Muir P, Navarro FCP, Parker A, Pei B, Pozo F, Ruffier M, Schmitt BM, Stapleton E, Suner MM, Sycheva I, Uszczynska-Ratajczak B, Xu J, Yates A, Zerbino D, Zhang Y, Aken B, Choudhary JS, Gerstein M, Guigo R, Hubbard TJP, Kellis M, Paten B, Reymond A, Tress ML, Flicek P (2018) GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res 47:D766–D773CrossRefGoogle Scholar
  16. Glazar P, Papavasileiou P, Rajewsky N (2014) circBase: a database for circular RNAs. RNA 20:1666–1670CrossRefGoogle Scholar
  17. Goettsch C, Rauner M, Pacyna N, Hempel U, Bornstein SR, Hofbauer LC (2011) miR-125b regulates calcification of vascular smooth muscle cells. Am J Pathol 179:1594–1600CrossRefGoogle Scholar
  18. Hadji F, Boulanger MC, Guay SP, Gaudreault N, Amellah S, Mkannez G, Bouchareb R, Marchand JT, Nsaibia MJ, Guauque-Olarte S, Pibarot P, Bouchard L, Bosse Y, Mathieu P (2016) Altered DNA methylation of long noncoding RNA H19 in Calcific aortic valve disease promotes mineralization by silencing NOTCH1. Circulation 134:1848–1862CrossRefGoogle Scholar
  19. Hajjari M, Salavaty A (2015) HOTAIR: an oncogenic long non-coding RNA in different cancers. Cancer Biol Med 12:1–9Google Scholar
  20. Hansen TB, Wiklund ED, Bramsen JB, Villadsen SB, Statham AL, Clark SJ, Kjems J (2011) miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. EMBO J 30:4414–4422CrossRefGoogle Scholar
  21. Howlett P, Cleal JK, Wu H, Shah N, Horton A, Curzen N, Mahmoudi M (2018) MicroRNA 8059 as a marker for the presence and extent of coronary artery calcification. Open Heart 5:e000678CrossRefGoogle Scholar
  22. Jeck WR, Sharpless NE (2014) Detecting and characterizing circular RNAs. Nat Biotechnol 32:453–461CrossRefGoogle Scholar
  23. Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, Marzluff WF, Sharpless NE (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 19:141–157CrossRefGoogle Scholar
  24. Karwowski W, Naumnik B, Szczepanski M, Mysliwiec M (2012) The mechanism of vascular calcification - a systematic review. Med Sci Monit 18:1–11CrossRefGoogle Scholar
  25. Kim YK (2015) Extracellular microRNAs as biomarkers in human disease. Chonnam Med J 51:51–57CrossRefGoogle Scholar
  26. Kim YK, Wee G, Park J, Kim J, Baek D, Kim JS, Kim VN (2013) TALEN-based knockout library for human microRNAs. Nat Struct Mol Biol 20:1458–1464CrossRefGoogle Scholar
  27. Kim YK, Kim B, Kim VN (2016) Re-evaluation of the roles of DROSHA, Export in 5, and DICER in microRNA biogenesis. Proc Natl Acad Sci USA 113:E1881–1889CrossRefGoogle Scholar
  28. Kind B, Muster B, Staroske W, Herce HD, Sachse R, Rapp A, Schmidt F, Koss S, Cardoso MC, Lee-Kirsch MA (2014) Altered spatio-temporal dynamics of RNase H2 complex assembly at replication and repair sites in Aicardi-Goutieres syndrome. Hum Mol Genet 23:5950–5960CrossRefGoogle Scholar
  29. Kleaveland B, Shi CY, Stefano J, Bartel DP (2018) A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain. Cell 174(350–362):e317Google Scholar
  30. Lanzer P, Boehm M, Sorribas V, Thiriet M, Janzen J, Zeller T, St Hilaire C, Shanahan C (2014) Medial vascular calcification revisited: review and perspectives. Eur Heart J 35:1515–1525CrossRefGoogle Scholar
  31. Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O, Fatica A, Santini T, Andronache A, Wade M, Laneve P, Rajewsky N, Bozzoni I (2017) Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis. Mol Cell 66(22–37):e29Google Scholar
  32. Li X, Yang L, Chen LL (2018) The biogenesis, functions, and challenges of circular RNAs. Mol Cell 71:428–442CrossRefGoogle Scholar
  33. Liao XB, Zhang ZY, Yuan K, Liu Y, Feng X, Cui RR, Hu YR, Yuan ZS, Gu L, Li SJ, Mao DA, Lu Q, Zhou XM, De Jesus Perez VA, Yuan LQ (2013) MiR-133a modulates osteogenic differentiation of vascular smooth muscle cells. Endocrinology 154:3344–3352CrossRefGoogle Scholar
  34. Liu J, Xiao X, Shen Y, Chen L, Xu C, Zhao H, Wu Y, Zhang Q, Zhong J, Tang Z, Liu C, Zhao Q, Zheng Y, Cao R, Zu X (2017) MicroRNA-32 promotes calcification in vascular smooth muscle cells: implications as a novel marker for coronary artery calcification. PLoS ONE 12:e0174138CrossRefGoogle Scholar
  35. Mao YS, Sunwoo H, Zhang B, Spector DL (2011) Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding RNAs. Nat Cell Biol 13:95–101CrossRefGoogle Scholar
  36. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, Loewer A, Ziebold U, Landthaler M, Kocks C, Le Noble F, Rajewsky N (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495:333–338CrossRefGoogle Scholar
  37. Pamudurti NR, Bartok O, Jens M, Ashwal-Fluss R, Stottmeister C, Ruhe L, Hanan M, Wyler E, Perez-Hernandez D, Ramberger E, Shenzis S, Samson M, Dittmar G, Landthaler M, Chekulaeva M, Rajewsky N, Kadener S (2017) Translation of CircRNAs. Mol Cell 66(9–21):e27Google Scholar
  38. Panizo S, Naves-Diaz M, Carrillo-Lopez N, Martinez-Arias L, Fernandez-Martin JL, Ruiz-Torres MP, Cannata-Andia JB, Rodriguez I (2016) MicroRNAs 29b, 133b, and 211 regulate vascular smooth muscle calcification mediated by high phosphorus. J Am Soc Nephrol 27:824–834CrossRefGoogle Scholar
  39. Piwecka M, Glazar P, Hernandez-Miranda LR, Memczak S, Wolf SA, Rybak-Wolf A, Filipchyk A, Klironomos F, Jara CCA, Jara CCA, Fenske P, Trimbuch T, Zywitza V, Plass M, Schreyer L, Ayoub S, Kocks C, Kuhn R, Rosenmund C, Birchmeier C, Rajewsky N (2017) Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science 357:eaam8526CrossRefGoogle Scholar
  40. Qiao W, Chen L, Zhang M (2014) MicroRNA-205 regulates the calcification and osteoblastic differentiation of vascular smooth muscle cells. Cell Physiol Biochem 33:1945–1953CrossRefGoogle Scholar
  41. Raveh E, Matouk IJ, Gilon M, Hochberg A (2015) The H19 Long non-coding RNA in cancer initiation, progression and metastasis - a proposed unifying theory. Mol Cancer 14:184CrossRefGoogle Scholar
  42. Rinn J, Guttman M (2014) RNA Function. RNA and dynamic nuclear organization. Science 345:1240–1241CrossRefGoogle Scholar
  43. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129:1311–1323CrossRefGoogle Scholar
  44. Rupaimoole R, Slack FJ (2017) MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 16:203–222CrossRefGoogle Scholar
  45. Sage AP, Tintut Y, Demer LL (2010) Regulatory mechanisms in vascular calcification. Nat Rev Cardiol 7:528–536CrossRefGoogle Scholar
  46. Sallam T, Sandhu J, Tontonoz P (2018) Long noncoding RNA discovery in cardiovascular disease: decoding form to function. Circ Res 122:155–166CrossRefGoogle Scholar
  47. Selleri L, Bartolomei MS, Bickmore WA, He L, Stubbs L, Reik W, Barsh GS (2016) A Hox-embedded long noncoding RNA: is it all hot air? PLoS Genet 12:e1006485CrossRefGoogle Scholar
  48. Shioi A, Nishizawa Y, Jono S, Koyama H, Hosoi M, Morii H (1995) Beta-glycerophosphate accelerates calcification in cultured bovine vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 15:2003–2009CrossRefGoogle Scholar
  49. Wang HJ, Zhang PJ, Chen WJ, Jie D, Dan F, Jia YH, Xie LX (2013) Characterization and Identification of novel serum microRNAs in sepsis patients with different outcomes. Shock 39:480–487CrossRefGoogle Scholar
  50. Wang J, Wang Y, Gu W, Ni B, Sun H, Yu T, Gu W, Chen L, Shao Y (2016) Comparative transcriptome analysis reveals substantial tissue specificity in human aortic valve. Evol Bioinform Online 12:175–184Google Scholar
  51. Wilson RC, Doudna JA (2013) Molecular mechanisms of RNA interference. Annu Rev Biophys 42:217–239CrossRefGoogle Scholar
  52. Yanagawa B, Lovren F, Pan Y, Garg V, Quan A, Tang G, Singh KK, Shukla PC, Kalra NP, Peterson MD, Verma S (2012) miRNA-141 is a novel regulator of BMP-2-mediated calcification in aortic stenosis. J Thorac Cardiovasc Surg 144:256–262CrossRefGoogle Scholar
  53. Yu C, Li L, Xie F, Guo S, Liu F, Dong N, Wang Y (2018) LncRNA TUG1 sponges miR-204-5p to promote osteoblast differentiation through upregulating Runx2 in aortic valve calcification. Cardiovasc Res 114:168–179CrossRefGoogle Scholar
  54. Zheng S, Zhang S, Song Y, Guo W, Zhai W, Qiu X, Li J (2016) MicroRNA-297a regulates vascular calcification by targeting fibroblast growth factor 23. Iran J Basic Med Sci 19:1331–1336Google Scholar

Copyright information

© The Pharmaceutical Society of Korea 2019

Authors and Affiliations

  1. 1.Department of BiochemistryChonnam National University Medical SchoolHwasunRepublic of Korea
  2. 2.Department of PharmacologyChonnam National University Medical SchoolHwasunRepublic of Korea
  3. 3.Basic Research Laboratory for Cardiac Remodeling Research LaboratoryChonnam National University Medical SchoolHwasunRepublic of Korea

Personalised recommendations