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Circulating miRNAs as biomarkers for endocrine disorders

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Abstract

Specific, sensitive and non-invasive biomarkers are always needed in endocrine disorders. miRNAs are short, non-coding RNA molecules with well-known role in gene expression regulation. They are frequently dysregulated in metabolic and endocrine diseases. Recently it has been shown that they are secreted into biofluids by nearly all kind of cell types. As they can be taken up by other cells they may have a role in a new kind of paracrine, cell-to-cell communication. Circulating miRNAs are protected by RNA-binding proteins or microvesicles hence they can be attractive candidates as diagnostic or prognostic biomarkers. In this review, we summarize the characteristics of extracellular miRNA’s and our knowledge about their origin and potential roles in endocrine and metabolic diseases. Discussions about the technical challenges occurring during identification and measurement of extracellular miRNAs and future perspectives about their roles are also highlighted.

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References

  1. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (2001) Identification of novel genes coding for small expressed RNAs. Science 294:853–858

    Article  PubMed  CAS  Google Scholar 

  2. Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R (2008) MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci USA 105:1608–1613

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  3. Orom UA, Nielsen FC, Lund AH (2008) MicroRNA-10a binds the 5′UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell 30:460–471

    Article  PubMed  CAS  Google Scholar 

  4. Zhang J, Guo H, Qian G, Ge S, Ji H, Hu X, Chen W (2010) MiR-145, a new regulator of the DNA fragmentation factor-45 (DFF45)-mediated apoptotic network. Mol Cancer 9:211

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, Shiekhattar R (2005) TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436:740–744

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R (2005) Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 123:631–640

    Article  PubMed  CAS  Google Scholar 

  7. Chen K, Rajewsky N (2006) Natural selection on human microRNA binding sites inferred from SNP data. Nat Genet 38:1452–1456

    Article  PubMed  CAS  Google Scholar 

  8. Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20

    Article  PubMed  CAS  Google Scholar 

  9. Mattick JS, Makunin IV (2005) Small regulatory RNAs in mammals. Hum Mol Genet. 14 Spec No 1:R121–R132

  10. Szabó PM, Butz H, Igaz P, Rácz K, Hunyady L, Patócs A (2013) Minireview: miRomics in endocrinology: a novel approach for modeling endocrine diseases. Mol Endocrinol 27:573–585

    Article  PubMed  CAS  Google Scholar 

  11. Farazi TA, Hoell JI, Morozov P, Tuschl T (2013) MicroRNAs in human cancer. Adv Exp Med Biol 774:1–20

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Rottiers V, Naar AM (2012) MicroRNAs in metabolism and metabolic disorders. Nat Rev Mol Cell Biol 13:239–250

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Sivapragasam M, Rotondo F, Lloyd RV, Scheithauer BW, Cusimano M, Syro LV, Kovacs K (2011) MicroRNAs in the human pituitary. Endocr Pathol 22:134–143

    Article  PubMed  CAS  Google Scholar 

  14. Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS, Hatton CS, Harris AL (2008) Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol 141:672–675

    Article  PubMed  Google Scholar 

  15. Silva J, García V, Zaballos Á, Provencio M, Lombardía L, Almonacid L, García JM, Domínguez G, Peña C, Diaz R, Herrera M, Varela A, Bonilla F (2011) Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival. Eur Respir J 37:617–623

    Article  PubMed  CAS  Google Scholar 

  16. Li X (2014) MiR-375, a microRNA related to diabetes. Gene 533:1–4

    Article  PubMed  CAS  Google Scholar 

  17. Hossain MM, Sohel MM, Schellander K, Tesfaye D (2012) Characterization and importance of microRNAs in mammalian gonadal functions. Cell Tissue Res 349:679–690

    Article  PubMed  CAS  Google Scholar 

  18. Lisse TS, Adams JS, Hewison M (2013) Vitamin D and microRNAs in bone. Crit Rev Eukaryot Gene Expr 23:195–214

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Pallante P, Battista S, Pierantoni GM, Fusco A (2014) Deregulation of microRNA expression in thyroid neoplasias. Nat Rev Endocrinol 10:88–101

    Article  PubMed  CAS  Google Scholar 

  20. Leone V, D’Angelo D, Ferraro A, Pallante P, Rubio I, Santoro M, Croce CM, Fusco A (2011) A TSH-CREB1-microRNA loop is required for thyroid cell growth. Mol Endocrinol 25:1819–1830

    Article  PubMed  CAS  Google Scholar 

  21. Singh P, Soon PS, Feige JJ, Chabre O, Zhao JT, Cherradi N, Lalli E, Sidhu SB (2012) Dysregulation of microRNAs in adrenocortical tumors. Mol Cell Endocrinol 351:118–128

    Article  PubMed  CAS  Google Scholar 

  22. Gadelha MR, Kasuki L, Dénes J, Trivellin G, Korbonits M (2013) MicroRNAs: suggested role in pituitary adenoma pathogenesis. J Endocrinol Invest 36:889–895

    Article  PubMed  CAS  Google Scholar 

  23. Zhang Z, Florez S, Gutierrez-Hartmann A, Martin JF, Amendt BA (2010) MicroRNAs regulate pituitary development, and microRNA 26b specifically targets lymphoid enhancer factor 1 (Lef-1), which modulates pituitary transcription factor 1 (Pit-1) expression. J Biol Chem 285:34718–34728

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. Lynn FC, Skewes-Cox P, Kosaka Y, McManus MT, Harfe BD, German MS (2007) MicroRNA expression is required for pancreatic islet cell genesis in the mouse. Diabetes 56:2938–2945

    Article  PubMed  CAS  Google Scholar 

  25. Correa-Medina M, Bravo-Egana V, Rosero S, Ricordi C, Edlund H, Diez J, Pastori RL (2009) MicroRNA miR-7 is preferentially expressed in endocrine cells of the developing and adult human pancreas. Gene Expr Patterns 9:193–199

    Article  PubMed  CAS  Google Scholar 

  26. Hong X, Luense LJ, McGinnis LK, Nothnick WB, Christenson LK (2008) Dicer1 is essential for female fertility and normal development of the female reproductive system. Endocrinology 149:6207–6212

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Mishra PJ, Merlino G (2009) MicroRNA reexpression as differentiation therapy in cancer. J Clin Invest 119:2119–2123

    PubMed  CAS  PubMed Central  Google Scholar 

  28. Mishra PJ, Humeniuk R, Mishra PJ, Longo-Sorbello GS, Banerjee D, Bertino JR (2007) A miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance. Proc Natl Acad Sci USA 104:13513–13518

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Mishra PJ, Bertino JR (2009) MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine. Pharmacogenomics 10:399–416

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  30. Mishra PJ, Song B, Mishra PJ, Wang Y, Humeniuk R, Banerjee D, Merlino G, Ju J, Bertino JR (2009) MiR-24 tumor suppressor activity is regulated independent of p53 and through a target site polymorphism. PLoS One 4:e8445

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. 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 56:1733–1741

    Article  PubMed  CAS  Google Scholar 

  32. Turchinovich A, Weiz L, Langheinz A, Burwinkel B (2011) Characterization of extracellular circulating microRNA. Nucleic Acids Res 39:7223–7233

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  34. Turchinovich A, Weiz L, Burwinkel B (2012) Extracellular miRNAs: the mystery of their origin and function. Trends Biochem Sci 37:460–465

    Article  PubMed  CAS  Google Scholar 

  35. 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 genetic exchange between cells. Nat Cell Biol 9:654–659

    Article  PubMed  CAS  Google Scholar 

  36. Krämer-Albers EM, Bretz N, Tenzer S, Winterstein C, Möbius W, Berger H, Nave KA, Schild H, Trotter J (2007) Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: trophic support for axons? Proteomics Clin Appl 1:1446–1461

    Article  PubMed  CAS  Google Scholar 

  37. Quesenberry PJ, Aliotta JM (2008) The paradoxical dynamism of marrow stem cells: considerations of stem cells, niches, and microvesicles. Stem Cell Rev 4:137–147

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Mallegol J, van NG, Heyman M (2005) Phenotypic and functional characterization of intestinal epithelial exosomes. Blood Cells Mol Dis 35:11–16

    Article  PubMed  CAS  Google Scholar 

  39. Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, Ricciardi-Castagnoli P, Raposo G, Amigorena S (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med 4:594–600

    Article  PubMed  CAS  Google Scholar 

  40. Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183:1161–1172

    Article  PubMed  CAS  Google Scholar 

  41. Thery C (2011) Exosomes: secreted vesicles and intercellular communications. F1000 Biol Rep 3:15

    Article  PubMed  PubMed Central  Google Scholar 

  42. Thery C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2:569–579

    PubMed  CAS  Google Scholar 

  43. Pigati L, Yaddanapudi SC, Iyengar R, Kim DJ, Hearn SA, Danforth D, Hastings ML, Duelli DM (2010) Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS One 5:e13515

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, Schwille P, Brügger B, Simons M (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319:1244–1247

    Article  PubMed  CAS  Google Scholar 

  45. Poutsiaka DD, Schroder EW, Taylor DD, Levy EM, Black PH (1985) Membrane vesicles shed by murine melanoma cells selectively inhibit the expression of Ia antigen by macrophages. J Immunol 134:138–144

    PubMed  CAS  Google Scholar 

  46. Kucharzewska P, Belting M (2013) Emerging roles of extracellular vesicles in the adaptive response of tumour cells to microenvironmental stress. J Extracell Vesicles 2:20304

    Article  Google Scholar 

  47. Kucharzewska P, Christianson HC, Welch JE, Svensson KJ, Fredlund E, Ringnér M, Mörgelin M, Bourseau-Guilmain E, Bengzon J, Belting M (2013) Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development. Proc Natl Acad Sci USA 110:7312–7317

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  48. Peinado H, Lavotshkin S, Lyden D (2011) The secreted factors responsible for pre-metastatic niche formation: old sayings and new thoughts. Semin Cancer Biol 21:139–146

    Article  PubMed  CAS  Google Scholar 

  49. Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT Jr, Carter BS, Krichevsky AM, Breakefield XO (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–1476

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  50. Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, Lovat F, Fadda P, Mao C, Nuovo GJ, Zanesi N, Crawford M, Ozer GH, Wernicke D, Alder H, Caligiuri MA, Nana-Sinkam P, Perrotti D, Croce CM (2012) MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci USA 109:E2110–E2116

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  51. Yang L, Wu X, Luo C, He Y, Zhang Y, Chen X, Zhang L, Chen L (2012) Effects of renal carcinoma cell line ACHN-derived exosomes on ACHN cell proliferation and apoptosis. Nan Fang Yi Ke Da Xue Xue Bao 32:1498–1502

    PubMed  CAS  Google Scholar 

  52. Ohshima K, Inoue K, Fujiwara A, Hatakeyama K, Kanto K, Watanabe Y, Muramatsu K, Fukuda Y, Ogura S, Yamaguchi K, Mochizuki T (2010) Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PLoS One 5:e13247

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006

    Article  PubMed  CAS  Google Scholar 

  54. Kroh EM, Parkin RK, Mitchell PS, Tewari M (2010) Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods 50:298–301

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  55. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 105:10513–10518

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  56. Laterza OF, Scott MG, Garrett-Engele PW, Korenblat KM, Lockwood CM (2013) Circulating miR-122 as a potential biomarker of liver disease. Biomark Med 7:205–210

    Article  PubMed  CAS  Google Scholar 

  57. Weng H, Shen C, Hirokawa G, Ji X, Takahashi R, Shimada K, Kishimoto C, Iwai N (2011) Plasma miR-124 as a biomarker for cerebral infarction. Biomed Res 32:135–141

    Article  PubMed  CAS  Google Scholar 

  58. Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L, Wagner DR, Staessen JA, Heymans S, Schroen B (2010) Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet 3:499–506

    Article  PubMed  Google Scholar 

  59. Teixeira AL, Ferreira M, Silva J, Gomes M, Dias F, Santos JI, Maurício J, Lobo F, Medeiros R (2014) Higher circulating expression levels of miR-221 associated with poor overall survival in renal cell carcinoma patients. Tumour Biol 35:4057–4066

    Article  PubMed  CAS  Google Scholar 

  60. Selth LA, Townley SL, Bert AG, Stricker PD, Sutherland PD, Horvath LG, Goodall GJ, Butler LM, Tilley WD (2013) Circulating microRNAs predict biochemical recurrence in prostate cancer patients. Br J Cancer 109:641–650

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  61. Tanaka K, Miyata H, Yamasaki M, Sugimura K, Takahashi T, Kurokawa Y, Nakajima K, Takiguchi S, Mori M, Doki Y (2013) Circulating miR-200c levels significantly predict response to chemotherapy and prognosis of patients undergoing neoadjuvant chemotherapy for esophageal cancer. Ann Surg Oncol 20(Suppl 3):S607–S615

    Article  PubMed  Google Scholar 

  62. Guay C, Regazzi R (2013) Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol 9:513–521

    Article  PubMed  CAS  Google Scholar 

  63. Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M (2010) Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res 107:810–817

    Article  PubMed  CAS  Google Scholar 

  64. Kong L, Zhu J, Han W, Jiang X, Xu M, Zhao Y, Dong Q, Pang Z, Guan Q, Gao L, Zhao J, Zhao L (2011) Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study. Acta Diabetol 48:61–69

    Article  PubMed  CAS  Google Scholar 

  65. Karolina DS, Tavintharan S, Armugam A, Sepramaniam S, Pek SL, Wong MT, Lim SC, Sum CF, Jeyaseelan K (2012) Circulating miRNA profiles in patients with metabolic syndrome. J Clin Endocrinol Metab 97:E2271–E2276

    Article  PubMed  CAS  Google Scholar 

  66. Zhang T, Lv C, Li L, Chen S, Liu S, Wang C, Su B (2013) Plasma miR-126 is a potential biomarker for early prediction of type 2 diabetes mellitus in susceptible individuals. Biomed Res Int 2013:761617

    PubMed  PubMed Central  Google Scholar 

  67. Nielsen LB, Wang C, Sørensen K, Bang-Berthelsen CH, Hansen L, Andersen ML, Hougaard P, Juul A, Zhang CY, Pociot F, Mortensen HB (2012) Circulating levels of microRNA from children with newly diagnosed type 1 diabetes and healthy controls: evidence that miR-25 associates to residual beta-cell function and glycaemic control during disease progression. Exp Diabetes Res 2012:896362

    PubMed  PubMed Central  Google Scholar 

  68. Sebastiani G, Grieco FA, Spagnuolo I, Galleri L, Cataldo D, Dotta F (2011) Increased expression of microRNA miR-326 in type 1 diabetic patients with ongoing islet autoimmunity. Diabetes Metab Res Rev 27:862–866

    Article  PubMed  CAS  Google Scholar 

  69. Salas-Pérez F, Codner E, Valencia E, Pizarro C, Carrasco E, Pérez-Bravo F (2013) MicroRNAs miR-21a and miR-93 are down regulated in peripheral blood mononuclear cells (PBMCs) from patients with type 1 diabetes. Immunobiology 218:733–737

    Article  PubMed  CAS  Google Scholar 

  70. Erener S, Mojibian M, Fox JK, Denroche HC, Kieffer TJ (2013) Circulating miR-375 as a biomarker of beta-cell death and diabetes in mice. Endocrinology 154:603–608

    Article  PubMed  CAS  Google Scholar 

  71. Prats-Puig A, Ortega FJ, Mercader JM, Moreno-Navarrete JM, Moreno M, Bonet N, Ricart W, López-Bermejo A, Fernández-Real JM (2013) Changes in circulating microRNAs are associated with childhood obesity. J Clin Endocrinol Metab 98:E1655–E1660

    Article  PubMed  CAS  Google Scholar 

  72. Wang YC, Li Y, Wang XY, Zhang D, Zhang H, Wu Q, He YQ, Wang JY, Zhang L, Xia H, Yan J, Li X, Ying H (2013) Circulating miR-130b mediates metabolic crosstalk between fat and muscle in overweight/obesity. Diabetologia 56:2275–2285

    Article  PubMed  CAS  Google Scholar 

  73. Cermelli S, Ruggieri A, Marrero JA, Ioannou GN, Beretta L (2011) Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease. PLoS One 6:e23937

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  74. Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT (2011) MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 13:423–433

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  75. Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S, Calin GA, Volinia S, Liu CG, Scarpa A, Croce CM (2006) MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol 24:4677–4684

    Article  PubMed  CAS  Google Scholar 

  76. Li SC, Essaghir A, Martijn C, Lloyd RV, Demoulin JB, Oberg K, Giandomenico V (2013) Global microRNA profiling of well-differentiated small intestinal neuroendocrine tumors. Mod Pathol 26:685–696

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  77. Li A, Yu J, Kim H, Wolfgang CL, Canto MI, Hruban RH, Goggins M (2013) MicroRNA array analysis finds elevated serum miR-1290 accurately distinguishes patients with low-stage pancreatic cancer from healthy and disease controls. Clin Cancer Res 19:3600–3610

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  78. Yu S, Liu Y, Wang J, Guo Z, Zhang Q, Yu F, Zhang Y, Huang K, Li Y, Song E, Zheng XL, Xiao H (2012) Circulating microRNA profiles as potential biomarkers for diagnosis of papillary thyroid carcinoma. J Clin Endocrinol Metab 97:2084–2092

    Article  PubMed  CAS  Google Scholar 

  79. Lee JC, Zhao JT, Clifton-Bligh RJ, Gill A, Gundara JS, Ip JC, Glover A, Sywak MS, Delbridge LW, Robinson BG, Sidhu SB (2013) MicroRNA-222 and microRNA-146b are tissue and circulating biomarkers of recurrent papillary thyroid cancer. Cancer 119:4358–4365

    Article  PubMed  CAS  Google Scholar 

  80. Lee YS, Lim YS, Lee JC, Wang SG, Park HY, Kim SY, Lee BJ (2015) Differential expression levels of plasma-derived miR-146b and miR-155 in papillary thyroid cancer. Oral Oncol 51:77–83

    Article  PubMed  CAS  Google Scholar 

  81. Cantara S, Pilli T, Sebastiani G, Cevenini G, Busonero G, Cardinale S, Dotta F, Pacini F (2014) Circulating miRNA95 and miRNA190 are sensitive markers for the differential diagnosis of thyroid nodules in a Caucasian population. J Clin Endocrinol Metab 99:4190–4198

    Article  PubMed  CAS  Google Scholar 

  82. Patel D, Boufraqech M, Jain M, Zhang L, He M, Gesuwan K, Gulati N, Nilubol N, Fojo T, Kebebew E (2013) MiR-34a and miR-483-5p are candidate serum biomarkers for adrenocortical tumors. Surgery 154:1224–1228

    Article  PubMed  Google Scholar 

  83. Szabó DR, Luconi M, Szabó PM, Tóth M, Szücs N, Horányi J, Nagy Z, Mannelli M, Patócs A, Rácz K, Igaz P (2014) Analysis of circulating microRNAs in adrenocortical tumors. Lab Invest 94:331–339

    Article  PubMed  CAS  Google Scholar 

  84. Chabre O, Libé R, Assie G, Barreau O, Bertherat J, Bertagna X, Feige JJ, Cherradi N (2013) Serum miR-483-5p and miR-195 are predictive of recurrence risk in adrenocortical cancer patients. Endocr Relat Cancer 20:579–594

    PubMed  CAS  Google Scholar 

  85. Palumbo T, Faucz FR, Azevedo M, Xekouki P, Iliopoulos D, Stratakis CA (2013) Functional screen analysis reveals miR-26b and miR-128 as central regulators of pituitary somatomammotrophic tumor growth through activation of the PTEN–AKT pathway. Oncogene 32:1651–1659

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  86. D’Angelo D, Palmieri D, Mussnich P, Roche M, Wierinckx A, Raverot G, Fedele M, Croce CM, Trouillas J, Fusco A (2012) Altered microRNA expression profile in human pituitary GH adenomas: down-regulation of miRNA targeting HMGA1, HMGA2, and E2F1. J Clin Endocrinol Metab 97:E1128–E1138

    Article  PubMed  CAS  Google Scholar 

  87. Butz H, Likó I, Czirják S, Igaz P, Korbonits M, Rácz K, Patócs A (2011) MicroRNA profile indicates downregulation of the TGFβ pathway in sporadic non-functioning pituitary adenomas. Pituitary 14:112–124

    Article  PubMed  CAS  Google Scholar 

  88. Gentilin E, Tagliati F, Filieri C, Molè D, Minoia M, Rosaria Ambrosio M, Degli Uberti EC, Zatelli MC (2013) miR-26a plays an important role in cell cycle regulation in ACTH-secreting pituitary adenomas by modulating protein kinase Cδ. Endocrinology 154:1690–1700

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  89. Qian ZR, Asa SL, Siomi H, Siomi MC, Yoshimoto K, Yamada S, Wang EL, Rahman MM, Inoue H, Itakura M, Kudo E, Sano T (2009) Overexpression of HMGA2 relates to reduction of the let-7 and its relationship to clinicopathological features in pituitary adenomas. Mod Pathol 22:431–441

    Article  PubMed  CAS  Google Scholar 

  90. Leone V, Langella C, D’Angelo D, Mussnich P, Wierinckx A, Terracciano L, Raverot G, Lachuer J, Rotondi S, Jaffrain-Rea ML, Trouillas J, Fusco A (2014) Mir-23b and miR-130b expression is downregulated in pituitary adenomas. Mol Cell Endocrinol 390:1–7

    Article  PubMed  CAS  Google Scholar 

  91. Butz H, Likó I, Czirják S, Igaz P, Khan MM, Zivkovic V, Bálint K, Korbonits M, Rácz K, Patócs A (2010) Down-regulation of Wee1 kinase by a specific subset of microRNA in human sporadic pituitary adenomas. J Clin Endocrinol Metab 95:E181–E191

    Article  PubMed  CAS  Google Scholar 

  92. Trivellin G, Butz H, Delhove J, Igreja S, Chahal HS, Zivkovic V, McKay T, Patócs A, Grossman AB, Korbonits M (2012) MicroRNA miR-107 is overexpressed in pituitary adenomas and inhibits the expression of aryl hydrocarbon receptor-interacting protein in vitro. Am J Physiol Endocrinol Metab 303:E708–E719

    Article  PubMed  CAS  Google Scholar 

  93. Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, Degli Uberti EC (2005) miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol 204:280–285

    Article  PubMed  CAS  Google Scholar 

  94. Amaral FC, Torres N, Saggioro F, Neder L, Machado HR, Silva WA Jr, Moreira AC, Castro M (2009) MicroRNAs differentially expressed in ACTH-secreting pituitary tumors. J Clin Endocrinol Metab 94:320–323

    Article  PubMed  CAS  Google Scholar 

  95. Bottoni A, Zatelli MC, Ferracin M, Tagliati F, Piccin D, Vignali C, Calin GA, Negrini M, Croce CM, Degli Uberti EC (2007) Identification of differentially expressed microRNAs by microarray: a possible role for microRNA genes in pituitary adenomas. J Cell Physiol 210:370–377

    Article  PubMed  CAS  Google Scholar 

  96. Mao ZG, He DS, Zhou J, Yao B, Xiao WW, Chen CH, Zhu YH, Wang HJ (2010) Differential expression of microRNAs in GH-secreting pituitary adenomas. Diagn Pathol 5:79

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  97. Wang C, Su Z, Sanai N, Xue X, Lu L, Chen Y, Wu J, Zheng W, Zhuge Q, Wu ZB (2012) microRNA expression profile and differentially-expressed genes in prolactinomas following bromocriptine treatment. Oncol Rep 27:1312–1320

    PubMed  CAS  Google Scholar 

  98. Di Ieva A, Butz H, Niamah M, Rotondo F, De Rosa S, Sav A, Yousef GM, Kovacs K, Cusimano MD (2014) MicroRNAs as biomarkers in pituitary tumors. Neurosurgery. 75:181–189

    Article  PubMed  Google Scholar 

  99. Wang Q, Li P, Li A, Jiang W, Wang H, Wang J, Xie K (2012) Plasma specific miRNAs as predictive biomarkers for diagnosis and prognosis of glioma. J Exp Clin Cancer Res 31:97

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  100. Patterson E, Webb R, Weisbrod A, Bian B, He M, Zhang L, Holloway AK, Krishna R, Nilubol N, Pacak K, Kebebew E (2012) The microRNA expression changes associated with malignancy and SDHB mutation in pheochromocytoma. Endocr Relat Cancer 19:157–166

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  101. Wang K, Yuan Y, Cho JH, McClarty S, Baxter D, Galas DJ (2012) Comparing the MicroRNA spectrum between serum and plasma. PLoS One 7:e41561

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  102. Pritchard CC, Kroh E, Wood B, Arroyo JD, Dougherty KJ, Miyaji MM, Tait JF, Tewari M (2012) Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies. Cancer Prev Res (Phila) 5:492–497

    Article  CAS  Google Scholar 

  103. Redova M, Poprach A, Nekvindova J, Iliev R, Radova L, Lakomy R, Svoboda M, Vyzula R, Slaby O (2012) Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinoma. J Transl Med 10:55

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  104. Sanders I, Holdenrieder S, Walgenbach-Brünagel G, von Ruecker A, Kristiansen G, Müller SC, Ellinger J (2012) Evaluation of reference genes for the analysis of serum miRNA in patients with prostate cancer, bladder cancer and renal cell carcinoma. Int J Urol 19:1017–1025

    Article  PubMed  CAS  Google Scholar 

  105. Zen K, Zhang CY (2012) Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human cancers. Med Res Rev 32:326–348

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study has been funded by “Lendület” grant provided to Attila Patocs by Hungarian Academy of Sciences.

Conflict of interest

The authors declare that there is no conflict of interest.

Ethical approval

All procedures performing in studies involving human participants were in accordance with the ethical standards of institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent of the present retrospective study was waived.

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Authors and Affiliations

  1. Hungarian Academy of Sciences and Semmelweis University Molecular Medicine Research Group, Budapest, Hungary

    H. Butz, K. Racz & A. Patocs

  2. 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, 46 Szentkirályi Str., Budapest, 1088, Hungary

    N. Kinga, K. Racz & A. Patocs

  3. Hungarian Academy of Sciences and Semmelweis University “Lendület” Hereditary Endocrine Tumors Research Group, Budapest, Hungary

    H. Butz & A. Patocs

Authors
  1. H. Butz
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  2. N. Kinga
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  3. K. Racz
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  4. A. Patocs
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Correspondence to A. Patocs.

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Butz, H., Kinga, N., Racz, K. et al. Circulating miRNAs as biomarkers for endocrine disorders. J Endocrinol Invest 39, 1–10 (2016). https://doi.org/10.1007/s40618-015-0316-5

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  • DOI: https://doi.org/10.1007/s40618-015-0316-5

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