Skip to main content

A Hypothesis of Circulating MicroRNAs’ Implication in High Incidence of Atrial Fibrillation and Other Electrocardiographic Abnormalities in Cancer Patients

  • Conference paper
  • First Online:
GeNeDis 2018

Abstract

MicroRNAs are short non-coding RNA molecules that control posttranscriptional gene expression and are present in tissues cells but also circulate in biological fluids in various forms (exosome, connected with proteins, apoptotic bodies, etc.). The roles that circulated extracellular serum microRNAs possess in cancer development, like in the delivery from a recipient cell to distant tissues and the repression of host genes resulting in the impairment of critical functions, are still undetermined. Disturbances, such as the higher incidence of atrial fibrillation in cancer patients, could be analyzed in the frame of suppressive action of circulated microRNAs in genes that control cardiac conduction in atrium. More precisely, mir-21 overexpression in tissues promotes atrium fibrosis and impairs conductibility. A possible hypothesis is that the high levels of circulating microRNA in cancer may exert the same effect. Further experiments are necessary to corroborate the hypothesis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adam O, Löhfelm B, Thum T, Gupta SK, Puhl SL, Schäfers HJ, Böhm M, Laufs U (2012) Role of mir-21 in the pathogenesis of atrial fibrosis. Basic Res Cardiol 107(5):278

    Article  PubMed  CAS  Google Scholar 

  • Alečković M, Kang Y (2015) Regulation of cancer metastasis by cell-free mirnas. Biochim Biophys Acta 1855(1):24–42

    PubMed  Google Scholar 

  • Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, Mitchell PS, Bennett CF, Pogosova-Agadjanyan EL, Stirewalt DL et al (2011) Argonaute2 complexes carry a population of circulating micrornas independent of vesicles in human plasma. Proc Natl Acad Sci 108(12):5003–5008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barana A, Matamoros M, Dolz-Gaitón P, Pérez-Hernández M, Amorós I, Núñez M, Sacristán S, Pedraz Á, Pinto Á, Fernández-Avilés F et al (2014) Chronic atrial fibrillation increases microrna-21 in human atrial myocytes decreasing l-type calcium current. Circ Arrhythm Electrophysiol 7(5):861–868

    Article  CAS  PubMed  Google Scholar 

  • Bartel DP (2004) Micrornas: genomics, biogenesis, mechanism, and function cell. Lit Rev Cell 116(2):281–297

    CAS  Google Scholar 

  • Callis TE, Pandya K, Seok HY, Tang RH, Tatsuguchi M, Huang ZP, Chen JF, Deng Z, Gunn B, Shumate J et al (2009) Microrna-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest 119(9):2772–2786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cañón S, Caballero R, Herraiz-Martínez A, Pérez-Hernández M, López B, Atienza F, Jalife J, Hove-Madsen L, Delpón E, Bernad A (2016) mir-208b upreg-ulation interferes with calcium handling in hl-1 atrial myocytes: implications in human chronic atrial fibrillation. J Mol Cell Cardiol 99:162–173

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X et al (2008) Characterization of micrornas in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18(10):997

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Wang W, Zhang Y, Chen Y, Hu T (2014) Predicting distant metastasis and chemoresistance using plasma mirnas. Med Oncol 31(1):799

    Article  PubMed  CAS  Google Scholar 

  • Chevillet JR, Kang Q, Ruf IK, Briggs HA, Vojtech LN, Hughes SM, Cheng HH, Arroyo JD, Meredith EK, Gallichotte EN et al (2014) Quantitative and stoichiometric analysis of the microrna content of exosomes. Proc Natl Acad Sci 111(41):14888–14893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiang DY, Zhang M, Voigt N, Alsina KM, Jakob H, Martin JF, Dobrev D, Wehrens XH, Li N (2015) Identification of microrna–mrna dysregulations in parox-ysmal atrial fibrillation. Int J Cardiol 184:190–197

    Article  PubMed  PubMed Central  Google Scholar 

  • Cioffi DL, Hubler TR, Scammell JG (2011) Organization and function of the fkbp52 and fkbp51 genes. Curr Opin Pharmacol 11(4):308–313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cui Y, Luan J, Li H, Zhou X, Han J (2016) Exosomes derived from mineralizing osteoblasts promote st2 cell osteogenic differentiation by alteration of microrna ex-pression. FEBS Lett 590(1):185–192

    Article  CAS  PubMed  Google Scholar 

  • Di Leva G, Garofalo M, Croce CM (2014) Micrornas in cancer. Ann Rev Pathol 9:287–314

    Article  CAS  Google Scholar 

  • Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, Lovat F, Fadda P, Mao C, Nuovo GJ et al (2012) Micrornas bind to toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci 109(31):E2110–E2116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fujita Y, Araya J, Ito S, Kobayashi K, Kosaka N, Yoshioka Y, Kadota T, Hara H, Kuwano K, Ochiya T (2015) Suppression of autophagy by extracellular vesicles promotes myofibroblast differentiation in copd pathogenesis. J Extracell Vesicles 4(1):28388

    Article  PubMed  CAS  Google Scholar 

  • Gabriely G, Wurdinger T, Kesari S, Esau CC, Burchard J, Linsley PS, Krichevsky AM (2008) Microrna 21 promotes glioma invasion by targeting matrix met-alloproteinase regulators. Mol Cell Biol 28(17):5369–5380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanke M, Hoefig K, Merz H, Feller AC, Kausch I, Jocham D, Warnecke JM, Sczakiel G (2010) A robust methodology to study urine microrna as tumor marker: microrna-126 and microrna-182 are related to urinary bladder cancer. In: Urologic oncology: seminars and original investigations. 28(6):655–661. ISSN 1078–1439, https://doi.org/10.1016/j.urolonc.2009.01.027. (http://www.sciencedirect.com/science/article/pii/S1078143909000313)

    Article  CAS  PubMed  Google Scholar 

  • He WA, Calore F, Londhe P, Canella A, Guttridge DC, Croce CM (2014) Mi-crovesicles containing mirnas promote muscle cell death in cancer cachexia via tlr7. Proc Natl Acad Sci 111(12):4525–4529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He Y, Lin J, Kong D, Huang M, Xu C, Kim TK, Etheridge A, Luo Y, Ding Y, Wang K (2015) Current state of circulating micrornas as cancer biomarkers. Clin Chem 61(9):1138–1155

    Article  CAS  PubMed  Google Scholar 

  • He X, Zhang K, Gao X, Li L, Tan H, Chen J, Zhou Y (2016) Rapid atrial pacing induces myocardial fibrosis by down-regulating smad7 via microrna-21 in rabbit. Heart Vessel 31(10):1696–1708

    Article  Google Scholar 

  • Hill L, Browne G, Tulchinsky E (2013) Zeb/mir-200 feedback loop: at the crossroads of signal transduction in cancer. Int J Cancer 132(4):745–754

    Article  CAS  PubMed  Google Scholar 

  • Huang Y, Shen XJ, Zou Q, Wang SP, Tang SM, Zhang GZ (2011) Biological functions of micrornas: a review. J Physiol Biochem 67(1):129–139

    Article  CAS  PubMed  Google Scholar 

  • Huang Z, Chen XJ, Qian C, Dong Q, Ding D, Wu QF, Li J, Wang HF, Li WH, Xie Q et al (2016) Signal transducer and activator of transcription 3/microrna-21 feedback loop contributes to atrial fibrillation by promoting atrial fibrosis in a rat sterile pericarditis model. Circ Arrhythm Electrophysiol 9(7):e003396

    Article  PubMed  PubMed Central  Google Scholar 

  • Kakimoto Y, Tanaka M, Kamiguchi H, Hayashi H, Ochiai E, Osawa M (2016) Mi-crorna deep sequencing reveals chamber-specific mir-208 family expression patterns in the human heart. Int J Cardiol 211:43–48

    Article  PubMed  Google Scholar 

  • Kim VN (2005) Microrna biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 6(5):376

    Article  CAS  PubMed  Google Scholar 

  • Kogure T, Lin WL, Yan IK, Braconi C, Patel T (2011) Intercellular nanovesicle-mediated microrna transfer: a mechanism of environmental modulation of hepato-cellular cancer cell growth. Hepatology 54(4):1237–1248

    Article  CAS  PubMed  Google Scholar 

  • Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microrna biogen-esis, function and decay. Nat Rev Genet 11(9):597

    Article  CAS  PubMed  Google Scholar 

  • Larrea E, Sole C, Manterola L, Goicoechea I, Armesto M, Arestin M, Caf-farel M, Araujo A, Araiz M, Fernandez-Mercado M et al (2016) New concepts in cancer biomarkers: circulating mirnas in liquid biopsies. Int J Mol Sci 17(5):627

    Article  PubMed Central  CAS  Google Scholar 

  • Le HB, Zhu WY, Chen DD, He JY, Huang YY, Liu XG, Zhang YK (2012) Evaluation of dynamic change of serum mir-21 and mir-24 in pre-and post-operative lung carcinoma patients. Med Oncol 29(5):3190–3197

    Article  CAS  PubMed  Google Scholar 

  • Liu H, Qin H, Chen GX, Liang MY, Rong J, Yao JP, Wu ZK (2014) Comparative expression profiles of microrna in left and right atrial appendages from patients with rheumatic mitral valve disease exhibiting sinus rhythm or atrial fibrillation. J Transl Med 12(1):90

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lu Y, Zhang Y, Wang N, Pan Z, Gao X, Zhang F, Zhang Y, Shan H, Luo X, Bai Y et al (2010) Microrna-328 contributes to adverse electrical remodeling in atrial fibrillation. Circulation 122(23):2378–2387

    Article  CAS  PubMed  Google Scholar 

  • Luo W, Li G, Yi Z, Nie Q, Zhang X (2016) E2f1-mir-20a-5p/20b-5p auto-regulatory feedback loop involved in myoblast proliferation and differentiation. Sci Rep 6(27904)

    Google Scholar 

  • Ma Y, Chen Y, Lin J, Liu Y, Luo K, Cao Y, Wang T, Jin H, Su Z, Wu H et al (2017) Circulating mir-31 as an effective biomarker for detection and prognosis of human cancer: a meta-analysis. Oncotarget 8(17):28660

    Article  PubMed  PubMed Central  Google Scholar 

  • Mao L, Li J, Chen WX, Cai YQ, Yu DD, Zhong SL, Zhao JH, Zhou JW, Tang JH (2016) Exosomes decrease sensitivity of breast cancer cells to adriamycin by delivering micrornas. Tumor Biol 37(4):5247–5256

    Article  CAS  Google Scholar 

  • Mause SF, Weber C (2010) Microparticles: protagonists of a novel communication net-work for intercellular information exchange. Circ Res 107(9):1047–1057

    Article  CAS  PubMed  Google Scholar 

  • Mery B, Guichard JB, Guy JB, Vallard A, Barthelemy JC, Da Costa A, Magné N, Bertoletti L (2017) Atrial fibrillation in cancer patients: hindsight, insight and foresight. Int J Cardiol 240:196–202

    Article  PubMed  Google Scholar 

  • Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A et al (2008) Circulating micrornas as stable blood-based markers for cancer detection. Proc Natl Acad Sci 105(30):10513–10518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montecalvo A, Larregina AT, Shufesky WJ, Stolz DB, Sullivan ML, Karls-son JM, Baty CJ, Gibson GA, Erdos G, Wang Z et al (2012) Mechanism of transfer of functional micrornas between mouse dendritic cells via exosomes. Blood 119(3):756–766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montgomery RL, Hullinger TG, Semus HM, Dickinson BA, Seto AG, Lynch JM, Stack C, Latimer PA, Olson EN, van Rooij E (2011) Therapeutic inhibition of mir-208a improves cardiac function and survival during heart failure. Circulation 24(14):1537–1547

    Article  CAS  Google Scholar 

  • Morishima M, Iwata E, Nakada C, Tsukamoto Y, Takanari H, Miyamoto S, Moriyama M, Ono K (2016) Atrial fibrillation-mediated upregulation of mir-30d regulates myocardial electrical remodeling of the g-protein-gated k+ channel, ik. ach. Circ J 80(6):1346–1355

    Article  PubMed  Google Scholar 

  • Nonaka R, Nishimura J, Kagawa Y, Osawa H, Hasegawa J, Murata K, Oka-mura S, Ota H, Uemura M, Hata T et al (2014) Circulating mir-199a-3p as a novel serum biomarker for colorectal cancer. Oncol Rep 32(6):2354–2358

    Article  CAS  PubMed  Google Scholar 

  • O’Neal WT, Lakoski SG, Qureshi W, Judd SE, Howard G, Howard VJ, Cushman M, Soliman EZ (2015) Relation between cancer and atrial fibrillation (from the reasons for geographic and racial differences in stroke study). Am J Cardiol 115(8):1090–1094

    Article  PubMed  PubMed Central  Google Scholar 

  • Perron MP, Provost P (2008) Protein interactions and complexes in human microrna biogenesis and function. Front Biosci 13:2537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reilly SN, Liu X, Carnicer R, Recalde A, Muszkiewicz A, Jayaram R, Carena MC, Wijesurendra R, Stefanini M, Surdo NC et al (2016) Up-regulation of mir-31 in human atrial fibrillation begets the arrhythmia by depleting dystrophin and neuronal nitric oxide synthase. Sci Transl Med 8(340):340ra74

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schotten U, Verheule S, Kirchhof P, Goette A (2011) Pathophysiological mechanisms of atrial fibrillation: a translational appraisal. Physiol Rev 91(1):265–325

    Article  PubMed  Google Scholar 

  • Selth L, Townley S, Bert A, Stricker P, Sutherland P, Horvath L, Goodall G, Butler L, Tilley W (2013) Circulating micrornas predict biochemical recurrence in prostate cancer patients. Br J Cancer 109(3):641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Skog J, Würdinger T, Van Rijn S, Meijer DH, Gainche L, Curry WT Jr, Carter BS, Krichevsky AM, Breakefield XO (2008) Glioblastoma microvesicles trans-port rna and proteins that promote tumour growth and provide diagnostic biomark-ers. Nat Cell Biol 10(12):1470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soares RJ, Cagnin S, Chemello F, Silvestrin M, Musaro A, De Pitta C, Lan-franchi G, Sandri M (2014) Involvement of mirnas in the regulation of muscle wasting during catabolic conditions. J Biol Chem 289(32):21909–21925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sohel MMH, Hoelker M, Noferesti SS, Salilew-Wondim D, Tholen E, Looft C, Rings F, Uddin MJ, Spencer TE, Schellander K et al (2013) Exosomal and non-exosomal transport of extra-cellular micrornas in follicular fluid: implications for bovine oocyte developmental competence. PLoS One 8(11):e785105

    Article  CAS  Google Scholar 

  • Souders CA, Bowers SL, Baudino TA (2009) Cardiac fibroblast: the renaissance cell. Circ Res 105(12):1164–1176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang Y, Cui Y, Li Z, Jiao Z, Zhang Y, He Y, Chen G, Zhou Q, Wang W, Zhou X et al (2016) Radiation-induced mir-208a increases the proliferation and radioresistance by targeting p21 in human lung cancer cells. J Exp Clin Cancer Res 35(1):7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tsukamoto M, Iinuma H, Yagi T, Matsuda K, Hashiguchi Y (2017) Circulating exo-somal microrna-21 as a biomarker in each tumor stage of colorectal cancer. Oncology 92(6):360–370

    Article  CAS  PubMed  Google Scholar 

  • Turchinovich A, Samatov TR, Tonevitsky AG, Burwinkel B (2013) Circulating mirnas: cell–cell communication function? Front Genet 4(119)

    Google Scholar 

  • Ulivi P, Foschi G, Mengozzi M, Scarpi E, Silvestrini R, Amadori D, Zoli W (2013) Peripheral blood mir-328 expression as a potential biomarker for the early diagnosis of nsclc. Int J Mol Sci 14(5):10332–10342

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007) Exosome-mediated transfer of mrnas and micrornas is a novel mechanism of ge-netic exchange between cells. Nat Cell Biol 9(6):654

    Article  CAS  PubMed  Google Scholar 

  • van den Berg NW, Kawasaki M, Berger WR, Neefs J, Meulendijks E, Tijsen AJ, de Groot JR (2017) Micrornas in atrial fibrillation: from expression signatures to functional implications. Cardiovasc Drugs Ther 31(3):345–365

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vickers KC, Remaley AT (2012) Lipid-based carriers of micrornas and intercellular communication. Curr Opin Lipidol 23(2):91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Wang Y, Han J, Li Y, Xie C, Xie L, Shi J, Zhang J, Yang B, Chen D et al (2015) Integrated analysis of microrna and mrna expression profiles in the left atrium of patients with nonvalvular paroxysmal atrial fibrillation: role of mir-146b-5p in atrial fibrosis. Heart Rhythm 12(5):1018–1026

    Article  CAS  PubMed  Google Scholar 

  • Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, Galas DJ, Wang K (2010) The microrna spectrum in 12 body fluids. Clin Chem 56(11):1733–1741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiong Q, Zhong Q, Zhang J, Yang M, Li C, Zheng P, Bi LJ, Ge F (2012) Iden-tification of novel mir-21 target proteins in multiple myeloma cells by quantitative proteomics. J Proteome Res 11(4):2078–2090

    Article  CAS  PubMed  Google Scholar 

  • Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L, Denecke B, Hristov M, Köppel T, Jahantigh MN, Lutgens E et al (2009) Delivery of microrna-126 by apoptotic bodies induces cxcl12-dependent vascular protection. Sci Signal 2(100):ra81–ra81

    Article  PubMed  Google Scholar 

  • Zhang Z, Yang J, Yan W, Li Y, Shen Z, Asahara T (2016) Pretreatment of cardiac stem cells with exosomes derived from mesenchymal stem cells enhances myocardial repair. J Am Heart Assoc 5(1):e002856

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Georgia Theocharopoulou .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Kapodistrias, N., Theocharopoulou, G., Vlamos, P. (2020). A Hypothesis of Circulating MicroRNAs’ Implication in High Incidence of Atrial Fibrillation and Other Electrocardiographic Abnormalities in Cancer Patients. In: Vlamos, P. (eds) GeNeDis 2018. Advances in Experimental Medicine and Biology, vol 1196. Springer, Cham. https://doi.org/10.1007/978-3-030-32637-1_1

Download citation

Publish with us

Policies and ethics