Skip to main content
SpringerLink
Log in

microRNA and Ovarian Cancer

  • Chapter
microRNA: Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 889))

Abstract

Ovarian cancer is the fifth most common cancer in women and the leading cause of death from gynaecological malignancy in the Western world. The majority of ovarian cancers are diagnosed at an advanced stage and this is due to lack of a reliable screening test and the vagueness of symptoms. Early diagnosis is key as the 5-year survival rate for women diagnosed with late-stage disease is less than 20 % compared to up to 90 % for women diagnosed at early-stage disease. Early-stage disease that has a good prognosis cannot be detected easily.

Currently, no standardized reliable screening test exists. Lack of a reliable screening test is due to the fact that the underlying molecular biology of oncogenesis in ovarian cancer is a complex pathway. Once the molecular biology of the ovarian cancer is known, more reliable and sensitive screening tests can be established and a better and effective treatment can be found. Current diagnostic tools include imaging and CA125 have their limitations in terms of accuracy.

There is a strong need for prognostic and predictive markers to diagnose it early and to help optimize and personalize treatment. microRNAs were recently found to be involved in the pathophysiology of all types of analyzed human cancers mainly by aberrant gene expression. microRNA profiling has allowed the identification of signatures associated with diagnosis, prognosis, and response to treatment of human tumors. Several studies showed that microRNAs are deregulated in ovarian cancer. This chapter reviews the role of microRNAs in ovarian cancer and their utility of microRNAs as diagnostic and prognostic markers for ovarian cancer

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

  1. Clarke DL. Screening for ovarian cancer. N Engl J Med. 2009;361:170–7.

    Article  Google Scholar 

  2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917.

    Article  CAS  PubMed  Google Scholar 

  3. Hensley M, Alektiar D, Chi D. Ovarian and fallopian-tube cancer. In: Barakat RR, Bevers MW, Gershenson D, Hoskins W, editors. Handbook of gynecologic oncology. London: Martin Dunitz; 2002.

    Google Scholar 

  4. Sueblinvong T, Carney ME. Current understanding of risk factors for ovarian cancer. Curr Treat Options Oncol. 2009;10:67–81.

    Article  PubMed  Google Scholar 

  5. Salehi F, Dunfield L, Phillips KP, Krewski D, Vanderhyden BC. Risk factors for ovarian cancer: an overview with emphasis on hormonal factors. J Toxicol Environ Health B Crit Rev. 2008;11(3-4):301–21.

    Article  CAS  PubMed  Google Scholar 

  6. Van Gorp T, Amant F, Neven P, Vergote I, Moerman P. Endometriosis and the development of malignant tumors of the pelvis. A review of literature. Best Pract Res Clin Obstet Gynaecol. 2004;18(2):349–71.

    Article  PubMed  Google Scholar 

  7. DeCherney AH, Nathan L, Laufer N. Premalignant and malignant disorders of the ovaries and oviducts. 9th ed. New York: Springer; 2003. p. 933–46.

    Google Scholar 

  8. Riman T, Nilsson S, Persson IR. Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies. Acta Obstet Gynecol Scand. 2004;83(9):783–95.

    Article  PubMed  Google Scholar 

  9. National Cancer Irish Registry. http://www.ncri.ie/.

  10. Reynolds K. Benign and malignant ovarian masses. In: Luesley DM, Baker PN, editors. Obstetrics and gynaecology. 1st ed. London: Hodder Arnold; 2004.

    Google Scholar 

  11. Tsai WC, Hsu SD, Hsu CS, Lai TC, Chen SJ, Shen R, et al. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Invest. 2012;122(8):2884–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yu M, Stott S, Toner M, Maheswaran S, Haber DA. Circulating tumor cells: approaches to isolation and characterization. J Cell Biol. 2011;192(3):373–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Clarke-Pearson DL. Clinical practice. Screening for ovarian cancer. N Engl J Med. 2009;361(2):170–7.

    Article  CAS  PubMed  Google Scholar 

  14. Santulli G, D’Ascia C. Atrial remodelling in echocardiographic super-responders to cardiac resynchronization therapy. Heart. 2012;98(6):517.

    Article  PubMed  Google Scholar 

  15. Moyer VA. Screening for ovarian cancer: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med. 2012;157(12):900–4.

    Article  PubMed  Google Scholar 

  16. Vang S, Wu HT, Fischer A, Miller DH, Maclaughlan S, Douglass E, et al. Identification of ovarian cancer metastatic miRNAs. PLoS One. 2013;8(3), e58226.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hankinson SHD, Colditz G, Willett W, Stampfer M, Rosner B, Hennekens C, Speizer F. Tubal ligation, hysterectomy, and risk of ovarian cancer. JAMA. 1993;270:2813–8.

    Article  CAS  PubMed  Google Scholar 

  18. Dietl J, Wischhusen J, Hausler SF. The post-reproductive Fallopian tube: better removed? Hum Reprod. 2011;26(11):2918–24.

    Article  CAS  PubMed  Google Scholar 

  19. Kahlert C, Kalluri R. Exosomes in tumor microenvironment influence cancer progression and metastasis. J Mol Med. 2013;91(4):431–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Couzin J. Cell biology: the ins and outs of exosomes. Science. 2005;308(5730):1862–3.

    Article  CAS  PubMed  Google Scholar 

  21. Thery C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9(8):581–93.

    Article  CAS  PubMed  Google Scholar 

  22. Taylor DD, Black PH. Shedding of plasma membrane fragments. Neoplastic and developmental importance. Dev Biol. 1986;3:33–57.

    CAS  Google Scholar 

  23. Taylor DD, Bohler HC, Gercel-Taylor C. Pregnancy-linked suppression of TcR signaling pathways by a circulating factor absent in recurrent spontaneous pregnancy loss (RPL). Mol Immunol. 2006;43(11):1872–80.

    Article  CAS  PubMed  Google Scholar 

  24. Landen Jr CN, Birrer MJ, Sood AK. Early events in the pathogenesis of epithelial ovarian cancer. J Clin Oncol. 2008;26(6):995–1005.

    Article  PubMed  CAS  Google Scholar 

  25. Shih IM, Kurman RJ. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol. 2004;164(5):1511–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Schorge JO, Modesitt SC, Coleman RL, Cohn DE, Kauff ND, Duska LR, et al. SGO White Paper on ovarian cancer: etiology, screening and surveillance. Gynecol Oncol. 2010;119(1):7–17.

    Article  PubMed  Google Scholar 

  27. Zhu C, Li J, Ding Q, Cheng G, Zhou H, Tao L, et al. miR-152 controls migration and invasive potential by targeting TGFalpha in prostate cancer cell lines. Prostate. 2013;73(10):1082–9.

    Article  CAS  PubMed  Google Scholar 

  28. Ginsberg SD. RNA amplification strategies for small sample populations. Methods. 2005;37(3):229–37.

    Article  CAS  PubMed  Google Scholar 

  29. Kacharmina JE, Crino PB, Eberwine J. Preparation of cDNA from single cells and subcellular regions. Methods Enzymol. 1999;303:3–18.

    Article  CAS  PubMed  Google Scholar 

  30. Che S, Ginesberg SD. Trends in RNA research. New York: Nova Science; 2006.

    Google Scholar 

  31. Fathalla MF. Incessant ovulation—a factor in ovarian neoplasia? Lancet. 1971;2(7716):163.

    Article  CAS  PubMed  Google Scholar 

  32. Cramer DW, Welch WR. Determinants of ovarian cancer risk. II. Inferences regarding pathogenesis. J Natl Cancer Inst. 1983;71(4):717–21.

    CAS  PubMed  Google Scholar 

  33. Qiao C, Yuan Z, Li J, He B, Zheng H, Mayer C, et al. Liver-specific microRNA-122 target sequences incorporated in AAV vectors efficiently inhibits transgene expression in the liver. Gene Ther. 2011;18(4):403–10.

    Article  CAS  PubMed  Google Scholar 

  34. Qi R, Weiland M, Gao XH, Zhou L, Mi QS. Identification of endogenous normalizers for serum microRNAs by microarray profiling: U6 small nuclear RNA is not a reliable normalizer. Hepatology. 2012;55(5):1640–2; author reply 2–3.

    Article  PubMed  Google Scholar 

  35. Debernardi S, Skoulakis S, Molloy G, Chaplin T, Dixon-McIver A, Young BD. MicroRNA miR-181a correlates with morphological sub-class of acute myeloid leukaemia and the expression of its target genes in global genome-wide analysis. Leukemia. 2007;21(5):912–6.

    CAS  PubMed  Google Scholar 

  36. Huober J, Meyer A, Wagner U, Wallwiener D. The role of neoadjuvant chemotherapy and interval laparotomy in advanced ovarian cancer. J Cancer Res Clin Oncol. 2002;128(3):153–60.

    Article  CAS  PubMed  Google Scholar 

  37. Chien JR, Aletti G, Bell DA, Keeney GL, Shridhar V, Hartmann LC. Molecular pathogenesis and therapeutic targets in epithelial ovarian cancer. J Cell Biochem. 2007;102(5):1117–29.

    Article  CAS  PubMed  Google Scholar 

  38. Teoh DG, Secord AA. Antiangiogenic therapies in epithelial ovarian cancer. Cancer Control. 2011;18(1):31–43.

    PubMed  Google Scholar 

  39. Suh DH, Kim K, Kim JW. Major clinical research advances in gynecologic cancer in 2011. J Gynecol Oncol. 2012;23(1):53–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Fishman DA, Cohen L, Blank SV, Shulman L, Singh D, Bozorgi K, et al. The role of ultrasound evaluation in the detection of early-stage epithelial ovarian cancer. Am J Obstet Gynecol. 2005;192(4):1214–21; discussion 21–2.

    Article  PubMed  Google Scholar 

  41. Menon U, Gentry-Maharaj A, Hallett R, Ryan A, Burnell M, Sharma A, et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol. 2009;10(4):327–40.

    Article  PubMed  Google Scholar 

  42. Jacobs IJ, Menon U. Progress and challenges in screening for early detection of ovarian cancer. Mol Cell Proteomics. 2004;3(4):355–66.

    Article  CAS  PubMed  Google Scholar 

  43. Partridge E, Kreimer AR, Greenlee RT, Williams C, Xu JL, Church TR, et al. Results from four rounds of ovarian cancer screening in a randomized trial. Obstet Gynecol. 2009;113(4):775–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Buys SS, Partridge E, Black A, Johnson CC, Lamerato L, Isaacs C, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011;305(22):2295–303.

    Article  CAS  PubMed  Google Scholar 

  45. Skates SJ, Jacobs IJ, Knapp RC. Tumor markers in screening for ovarian cancer. Methods Mol Med. 2001;39:61–73.

    CAS  PubMed  Google Scholar 

  46. Bast Jr RC, Klug TL, St John E, Jenison E, Niloff JM, Lazarus H, et al. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med. 1983;309(15):883–7.

    Article  PubMed  Google Scholar 

  47. Gocze P, Vahrson H. [Ovarian carcinoma antigen (CA 125) and ovarian cancer (clinical follow-up and prognostic studies)]. Orv Hetil. 1993;134(17):915–8.

    CAS  PubMed  Google Scholar 

  48. Santillan A, Garg R, Zahurak ML, Gardner GJ, Giuntoli 2nd RL, Armstrong DK, et al. Risk of epithelial ovarian cancer recurrence in patients with rising serum CA-125 levels within the normal range. J Clin Oncol. 2005;23(36):9338–43.

    Article  PubMed  Google Scholar 

  49. Gupta D, Lis CG. Role of CA125 in predicting ovarian cancer survival—a review of the epidemiological literature. J Ovarian Res. 2009;2:13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Helzlsouer KJ, Bush TL, Alberg AJ, Bass KM, Zacur H, Comstock GW. Prospective study of serum CA-125 levels as markers of ovarian cancer. JAMA. 1993;269(9):1123–6.

    Article  CAS  PubMed  Google Scholar 

  51. Gadducci A, Cosio S, Carpi A, Nicolini A, Genazzani AR. Serum tumor markers in the management of ovarian, endometrial and cervical cancer. Biomed Pharmacother. 2004;58(1):24–38.

    Article  CAS  PubMed  Google Scholar 

  52. Gadducci A, Ferdeghini M, Prontera C, Moretti L, Mariani G, Bianchi R, et al. The concomitant determination of different tumor markers in patients with epithelial ovarian cancer and benign ovarian masses: relevance for differential diagnosis. Gynecol Oncol. 1992;44(2):147–54.

    Article  CAS  PubMed  Google Scholar 

  53. Koelma IA, Nap M, Rodenburg CJ, Fleuren GJ. The value of tumor marker CA 125 in surgical pathology. Histopathology. 1987;11(3):287–94.

    Article  CAS  PubMed  Google Scholar 

  54. Kudoh K, Kikuchi Y, Kita T, Tode T, Takano M, Hirata J, et al. Preoperative determination of several serum tumor markers in patients with primary epithelial ovarian carcinoma. Gynecol Obstet Invest. 1999;47(1):52–7.

    Article  CAS  PubMed  Google Scholar 

  55. Negishi Y, Furukawa T, Oka T, Sakamoto M, Hirata T, Okabe K, et al. Clinical use of CA 125 and its combination assay with other tumor marker in patients with ovarian carcinoma. Gynecol Obstet Invest. 1987;23(3):200–7.

    Article  CAS  PubMed  Google Scholar 

  56. Castelli M, Battaglia F, Scambia G, Panici PB, Ferrandina G, Mileo AM, et al. Immunosuppressive acidic protein and CA 125 levels in patients with ovarian cancer. Oncology. 1991;48(1):13–7.

    Article  CAS  PubMed  Google Scholar 

  57. Castelli M, Romano P, Atlante G, Pozzi M, Ferrini U. Immunosuppressive acidic protein (IAP) and CA 125 assays in detection of human ovarian cancer: preliminary results. Int J Biol Markers. 1987;2(3):187–90.

    CAS  PubMed  Google Scholar 

  58. Fioretti P, Gadducci A, Ferdeghini M, Prontera C, Malagnino G, Facchini V, et al. The concomitant determination of different serum tumor markers in epithelial ovarian cancer: relevance for monitoring the response to chemotherapy and follow-up of patients. Gynecol Oncol. 1992;44(2):155–60.

    Article  CAS  PubMed  Google Scholar 

  59. Negishi Y, Iwabuchi H, Sakunaga H, Sakamoto M, Okabe K, Sato H, et al. Serum and tissue measurements of CA72-4 in ovarian cancer patients. Gynecol Oncol. 1993;48(2):148–54.

    Article  CAS  PubMed  Google Scholar 

  60. Sawada M, Okudaira Y, Matsui Y, Shimizu Y. Immunosuppressive acidic protein in patients with ovarian cancer. Cancer. 1983;52(11):2081–5.

    Article  CAS  PubMed  Google Scholar 

  61. Yedema C, Massuger L, Hilgers J, Servaas J, Poels L, Thomas C, et al. Pre-operative discrimination between benign and malignant ovarian tumors using a combination of CA125 and CA15.3 serum assays. Int J Cancer Suppl. 1988;3:61–7.

    Article  CAS  PubMed  Google Scholar 

  62. Onsrud M. Tumor markers in gynaecologic oncology. Scand J Clin Lab Invest Suppl. 1991;206:60–70.

    Article  CAS  PubMed  Google Scholar 

  63. Roman LD, Muderspach LI, Burnett AF, Morrow CP. Carcinoembryonic antigen in women with isolated pelvic masses. Clinical utility? J Reprod Med. 1998;43(5):403–7.

    CAS  PubMed  Google Scholar 

  64. Kobayashi E, Ueda Y, Matsuzaki S, Yokoyama T, Kimura T, Yoshino K, et al. Biomarkers for screening, diagnosis, and monitoring of ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2012;21(11):1902–12.

    Article  CAS  PubMed  Google Scholar 

  65. Gadducci A, Ferdeghini M, Ceccarini T, Prontera C, Facchini V, Bianchi R, et al. A comparative evaluation of the ability of serum CA 125, CA 19-9, CA 15-3, CA 50, CA 72-4 and TATI assays in reflecting the course of disease in patients with ovarian carcinoma. Eur J Gynaecol Oncol. 1990;11(2):127–33.

    CAS  PubMed  Google Scholar 

  66. Gao L, Cheng HY, Dong L, Ye X, Liu YN, Chang XH, et al. The role of HE4 in ovarian cancer: inhibiting tumor cell proliferation and metastasis. J Int Med Res. 2011;39(5):1645–60.

    Article  CAS  PubMed  Google Scholar 

  67. Andersen MR, Goff BA, Lowe KA, Scholler N, Bergan L, Drescher CW, et al. Use of a Symptom Index, CA125, and HE4 to predict ovarian cancer. Gynecol Oncol. 2010;116(3):378–83.

    Article  PubMed  Google Scholar 

  68. Montagnana M, Danese E, Giudici S, Franchi M, Guidi GC, Plebani M, et al. HE4 in ovarian cancer: from discovery to clinical application. Adv Clin Chem. 2011;55:1–20.

    Article  CAS  PubMed  Google Scholar 

  69. Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 2005;65(6):2162–9.

    Article  CAS  PubMed  Google Scholar 

  70. Van Gorp T, Cadron I, Despierre E, Daemen A, Leunen K, Amant F, et al. HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm. Br J Cancer. 2011;104(5):863–70.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Moore RG, Brown AK, Miller MC, Skates S, Allard WJ, Verch T, et al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 2008;108(2):402–8.

    Article  CAS  PubMed  Google Scholar 

  72. Kalapotharakos G, Asciutto C, Henic E, Casslen B, Borgfeldt C. High preoperative blood levels of HE4 predicts poor prognosis in patients with ovarian cancer. J Ovarian Res. 2012;5(1):20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Angioli R, Plotti F, Capriglione S, Aloisi A, Montera R, Luvero D, et al. Can the preoperative HE4 level predict optimal cytoreduction in patients with advanced ovarian carcinoma? Gynecol Oncol. 2013;128(3):579–83.

    Article  CAS  PubMed  Google Scholar 

  74. Paek J, Lee SH, Yim GW, Lee M, Kim YJ, Nam EJ, et al. Prognostic significance of human epididymis protein 4 in epithelial ovarian cancer. Eur J Obstet Gynecol Reprod Biol. 2011;158(2):338–42.

    Article  CAS  PubMed  Google Scholar 

  75. Kong SY, Han MH, Yoo HJ, Hwang JH, Lim MC, Seo SS, et al. Serum HE4 level is an independent prognostic factor in epithelial ovarian cancer. Ann Surg Oncol. 2012;19(5):1707–12.

    Article  PubMed  Google Scholar 

  76. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, et al. MicroRNA signatures in human ovarian cancer. Cancer Res. 2007;67(18):8699–707.

    Article  CAS  PubMed  Google Scholar 

  77. Calin GA, Croce CM. MicroRNA-cancer connection: the beginning of a new tale. Cancer Res. 2006;66(15):7390–4.

    Article  CAS  PubMed  Google Scholar 

  78. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.

    Article  CAS  PubMed  Google Scholar 

  79. Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69.

    Article  CAS  PubMed  Google Scholar 

  80. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99(24):15524–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005;65(14):6029–33.

    Article  CAS  PubMed  Google Scholar 

  82. He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, et al. The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci U S A. 2005;102(52):19075–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004;64(11):3753–6.

    Article  CAS  PubMed  Google Scholar 

  84. Zhang L, Huang J, Yang N, Greshock J, Megraw MS, Giannakakis A, et al. microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci U S A. 2006;103(24):9136–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102(39):13944–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Michael MZ, O’Connor SM, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 2003;1(12):882–91.

    CAS  PubMed  Google Scholar 

  87. Chung YW, Bae HS, Song JY, Lee JK, Lee NW, Kim T, et al. Detection of MicroRNA as novel biomarkers of epithelial ovarian cancer from the serum of ovarian cancer patient. Int J Gynecol Cancer. 2013;23:673–9.

    Article  PubMed  Google Scholar 

  88. Qin W, Ren Q, Liu T, Huang Y, Wang J. MicroRNA-155 is a novel suppressor of ovarian cancer-initiating cells that targets CLDN1. FEBS Lett. 2013;587(9):1434–9.

    Article  CAS  PubMed  Google Scholar 

  89. He J, Jing Y, Li W, Qian X, Xu Q, Li FS, et al. Roles and mechanism of miR-199a and miR-125b in tumor angiogenesis. PLoS One. 2013;8(2):e56647.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Flavin RJ, Smyth PC, Finn SP, Laios A, O’Toole SA, Barrett C, et al. Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients. Mod Pathol. 2008;21(6):676–84.

    Article  CAS  PubMed  Google Scholar 

  91. Merritt WM, Lin YG, Han LY, Kamat AA, Spannuth WA, Schmandt R, et al. Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med. 2008;359(25):2641–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Laios A, O’Toole S, Flavin R, Martin C, Kelly L, Ring M, et al. Potential role of miR-9 and miR-223 in recurrent ovarian cancer. Mol Cancer. 2008;7:35.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Nam EJ, Yoon H, Kim SW, Kim H, Kim YT, Kim JH, et al. MicroRNA expression profiles in serous ovarian carcinoma. Clin Cancer Res. 2008;14(9):2690–5.

    Article  CAS  PubMed  Google Scholar 

  94. Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N, et al. Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci U S A. 2008;105(19):7004–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Eitan R, Kushnir M, Lithwick-Yanai G, David MB, Hoshen M, Glezerman M, et al. Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients. Gynecol Oncol. 2009;114(2):253–9.

    Article  CAS  PubMed  Google Scholar 

  96. Gallagher MF, Flavin RJ, Elbaruni SA, McInerney JK, Smyth PC, Salley YM, et al. Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients. J Ovarian Res. 2009;2:19.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Lee CH, Subramanian S, Beck AH, Espinosa I, Senz J, Zhu SX, et al. MicroRNA profiling of BRCA1/2 mutation-carrying and non-mutation-carrying high-grade serous carcinomas of ovary. PLoS One. 2009;4(10), e7314.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Wyman SK, Parkin RK, Mitchell PS, Fritz BR, O’Briant K, Godwin AK, et al. Repertoire of microRNAs in epithelial ovarian cancer as determined by next generation sequencing of small RNA cDNA libraries. PLoS One. 2009;4(4), e5311.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Sorrentino A, Liu CG, Addario A, Peschle C, Scambia G, Ferlini C. Role of microRNAs in drug-resistant ovarian cancer cells. Gynecol Oncol. 2008;111(3):478–86.

    Article  CAS  PubMed  Google Scholar 

  100. Yang N, Kaur S, Volinia S, Greshock J, Lassus H, Hasegawa K, et al. MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Res. 2008;68(24):10307–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Yang H, Kong W, He L, Zhao JJ, O’Donnell JD, Wang J, et al. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 2008;68(2):425–33.

    Article  CAS  PubMed  Google Scholar 

  102. Zhu CL, Gao GS. miR-200a overexpression in advanced ovarian carcinomas as a prognostic indicator. Asian Pac J Cancer Prev. 2014;15(20):8595–601.

    Article  PubMed  Google Scholar 

  103. Hu X, Macdonald DM, Huettner PC, Feng Z, El Naqa IM, Schwarz JK, et al. A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer. Gynecol Oncol. 2009;114(3):457–64.

    Article  CAS  PubMed  Google Scholar 

  104. Marchini S, Cavalieri D, Fruscio R, Calura E, Garavaglia D, Nerini IF, et al. Association between miR-200c and the survival of patients with stage I epithelial ovarian cancer: a retrospective study of two independent tumor tissue collections. Lancet Oncol. 2011;12(3):273–85.

    Article  CAS  PubMed  Google Scholar 

  105. Cochrane DR, Spoelstra NS, Howe EN, Nordeen SK, Richer JK. MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. Mol Cancer Ther. 2009;8(5):1055–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Kan CW, Hahn MA, Gard GB, Maidens J, Huh JY, Marsh DJ, et al. Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer. BMC Cancer. 2012;12:627.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Dahiya N, Sherman-Baust CA, Wang TL, Davidson B, Shih Ie M, Zhang Y, et al. MicroRNA expression and identification of putative miRNA targets in ovarian cancer. PLoS One. 2008;3(6), e2436.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Viswanathan SR, Daley GQ, Gregory RI. Selective blockade of microRNA processing by Lin28. Science. 2008;320(5872):97–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Lu L, Katsaros D, Shaverdashvili K, Qian B, Wu Y, de la Longrais IA, et al. Pluripotent factor lin-28 and its homologue lin-28b in epithelial ovarian cancer and their associations with disease outcomes and expression of let-7a and IGF-II. Eur J Cancer. 2009;45(12):2212–8.

    Article  CAS  PubMed  Google Scholar 

  110. Tang Z, Ow GS, Thiery JP, Ivshina AV, Kuznetsov VA. Meta-analysis of transcriptome reveals let-7b as an unfavorable prognostic biomarker and predicts molecular and clinical subclasses in high-grade serous ovarian carcinoma. Int J Cancer. 2014;134(2):306–18.

    Article  PubMed  CAS  Google Scholar 

  111. Bussing I, Slack FJ, Grosshans H. let-7 microRNAs in development, stem cells and cancer. Trends Mol Med. 2008;14(9):400–9.

    Article  PubMed  CAS  Google Scholar 

  112. Brueckner B, Stresemann C, Kuner R, Mund C, Musch T, Meister M, et al. The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function. Cancer Res. 2007;67(4):1419–23.

    Article  CAS  PubMed  Google Scholar 

  113. Lu L, Katsaros D, de la Longrais IA, Sochirca O, Yu H. Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-II expression and favorable prognosis. Cancer Res. 2007;67(21):10117–22.

    Article  CAS  PubMed  Google Scholar 

  114. van Jaarsveld MT, Helleman J, Berns EM, Wiemer EA. MicroRNAs in ovarian cancer biology and therapy resistance. Int J Biochem Cell Biol. 2010;42(8):1282–90.

    Article  PubMed  CAS  Google Scholar 

  115. Koutsaki M, Spandidos DA, Zaravinos A. Epithelial-mesenchymal transition-associated miRNAs in ovarian carcinoma, with highlight on the miR-200 family: prognostic value and prospective role in ovarian cancer therapeutics. Cancer Lett. 2014;351(2):173–81.

    Article  CAS  PubMed  Google Scholar 

  116. Chen J, Wang L, Matyunina LV, Hill CG, McDonald JF. Overexpression of miR-429 induces mesenchymal-to-epithelial transition (MET) in metastatic ovarian cancer cells. Gynecol Oncol. 2011;121(1):200–5.

    Article  CAS  PubMed  Google Scholar 

  117. Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22(7):894–907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Xu S, Xu P, Wu W, Ou Y, Xu J, Zhang G, et al. The biphasic expression pattern of miR-200a and E-cadherin in epithelial ovarian cancer and its correlation with clinicopathological features. Curr Pharm Des. 2014;20(11):1888–95.

    Article  CAS  PubMed  Google Scholar 

  119. Banno K, Yanokura M, Iida M, Adachi M, Nakamura K, Nogami Y, et al. Application of microRNA in diagnosis and treatment of ovarian cancer. BioMed Res Int. 2014;2014:232817.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Boyerinas B, Park SM, Murmann AE, Gwin K, Montag AG, Zillhardt M, et al. Let-7 modulates acquired resistance of ovarian cancer to Taxanes via IMP-1-mediated stabilization of multidrug resistance 1. Int J Cancer. 2012;130(8):1787–97.

    Article  CAS  PubMed  Google Scholar 

  121. Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 2009;1796(2):75–90.

    CAS  PubMed  Google Scholar 

  122. Zhou X, Hu Y, Dai L, Wang Y, Zhou J, Wang W, et al. MicroRNA-7 inhibits tumor metastasis and reverses epithelial-mesenchymal transition through AKT/ERK1/2 inactivation by targeting EGFR in epithelial ovarian cancer. PLoS One. 2014;9(5), e96718.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Tang H, Yao L, Tao X, Yu Y, Chen M, Zhang R, et al. miR-9 functions as a tumor suppressor in ovarian serous carcinoma by targeting TLN1. Int J Mol Med. 2013;32(2):381–8.

    CAS  PubMed  Google Scholar 

  124. Bhattacharya R, Nicoloso M, Arvizo R, Wang E, Cortez A, Rossi S, et al. MiR-15a and MiR-16 control Bmi-1 expression in ovarian cancer. Cancer Res. 2009;69(23):9090–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ. 2010;17(2):215–20.

    Article  CAS  PubMed  Google Scholar 

  126. Li J, Liang S, Yu H, Zhang J, Ma D, Lu X. An inhibitory effect of miR-22 on cell migration and invasion in ovarian cancer. Gynecol Oncol. 2010;119(3):543–8.

    Article  CAS  PubMed  Google Scholar 

  127. Wang Z, Ting Z, Li Y, Chen G, Lu Y, Hao X. microRNA-199a is able to reverse cisplatin resistance in human ovarian cancer cells through the inhibition of mammalian target of rapamycin. Oncol Lett. 2013;6(3):789–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Flavin R, Smyth P, Barrett C, Russell S, Wen H, Wei J, et al. miR-29b expression is associated with disease-free survival in patients with ovarian serous carcinoma. Int J Gynecol Cancer. 2009;19(4):641–7.

    Article  PubMed  Google Scholar 

  129. Creighton CJ, Hernandez-Herrera A, Jacobsen A, Levine DA, Mankoo P, Schultz N, et al. Integrated analyses of microRNAs demonstrate their widespread influence on gene expression in high-grade serous ovarian carcinoma. PLoS One. 2012;7(3), e34546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A. 2007;104(40):15805–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, et al. MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood. 2009;113(25):6411–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Zhang Q, He XJ, Ma LP, Li N, Yang J, Cheng YX, et al. Expression and significance of microRNAs in the p53 pathway in ovarian cancer cells and serous ovarian cancer tissues. Zhonghua Zhong Liu ZA Zhi. 2011;33(12):885–90 [Chinese Journal of Oncology].

    CAS  PubMed  Google Scholar 

  133. Corney DC, Hwang CI, Matoso A, Vogt M, Flesken-Nikitin A, Godwin AK, et al. Frequent downregulation of miR-34 family in human ovarian cancers. Clin Cancer Res. 2010;16(4):1119–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Zhou X, Zhao F, Wang ZN, Song YX, Chang H, Chiang Y, et al. Altered expression of miR-152 and miR-148a in ovarian cancer is related to cell proliferation. Oncol Rep. 2012;27(2):447–54.

    CAS  PubMed  Google Scholar 

  135. Zhang H, Wang Q, Zhao Q, Di W. MiR-124 inhibits the migration and invasion of ovarian cancer cells by targeting SphK1. J Ovarian Res. 2013;6(1):84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Wang W, Ren F, Wu Q, Jiang D, Li H, Shi H. MicroRNA-497 suppresses angiogenesis by targeting vascular endothelial growth factor A through the PI3K/AKT and MAPK/ERK pathways in ovarian cancer. Oncol Rep. 2014;32(5):2127–33.

    CAS  PubMed  Google Scholar 

  137. Zaman MS, Maher DM, Khan S, Jaggi M, Chauhan SC. Current status and implications of microRNAs in ovarian cancer diagnosis and therapy. J Ovarian Res. 2012;5(1):44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Peng DX, Luo M, Qiu LW, He YL, Wang XF. Prognostic implications of microRNA-100 and its functional roles in human epithelial ovarian cancer. Oncol Rep. 2012;27(4):1238–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Nagaraja AK, Creighton CJ, Yu Z, Zhu H, Gunaratne PH, Reid JG, et al. A link between mir-100 and FRAP1/mTOR in clear cell ovarian cancer. Mol Endocrinol. 2010;24(2):447–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Mabuchi S, Kawase C, Altomare DA, Morishige K, Sawada K, Hayashi M, et al. mTOR is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary. Clin Cancer Res. 2009;15(17):5404–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Luo J, Zhou J, Cheng Q, Zhou C, Ding Z. Role of microRNA-133a in epithelial ovarian cancer pathogenesis and progression. Oncol Lett. 2014;7(4):1043–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Guo J, Xia B, Meng F, Lou G. miR-133a suppresses ovarian cancer cell proliferation by directly targeting insulin-like growth factor 1 receptor. Tumor Biol. 2014;35(2):1557–64.

    Article  CAS  Google Scholar 

  143. Wu H, Xiao Z, Wang K, Liu W, Hao Q. MiR-145 is downregulated in human ovarian cancer and modulates cell growth and invasion by targeting p70S6K1 and MUC1. Biochem Biophys Res Commun. 2013;441(4):693–700.

    Article  CAS  PubMed  Google Scholar 

  144. Zhang W, Wang Q, Yu M, Wu N, Wang H. MicroRNA-145 function as a cell growth repressor by directly targeting c-Myc in human ovarian cancer. Technol Cancer Res Treat. 2014;13(2):161–8.

    CAS  PubMed  Google Scholar 

  145. Xu Q, Liu LZ, Qian X, Chen Q, Jiang Y, Li D, et al. MiR-145 directly targets p70S6K1 in cancer cells to inhibit tumor growth and angiogenesis. Nucleic Acids Res. 2012;40(2):761–74.

    Article  CAS  PubMed  Google Scholar 

  146. Wang S, Zhao X, Wang J, Wen Y, Zhang L, Wang D, et al. Upregulation of microRNA-203 is associated with advanced tumor progression and poor prognosis in epithelial ovarian cancer. Med Oncol. 2013;30(3):681.

    Article  CAS  PubMed  Google Scholar 

  147. Yu X, Zhang X, Bi T, Ding Y, Zhao J, Wang C, et al. MiRNA expression signature for potentially predicting the prognosis of ovarian serous carcinoma. Tumor Biol. 2013;34(6):3501–8.

    Article  CAS  Google Scholar 

  148. Lou Y, Yang X, Wang F, Cui Z, Huang Y. MicroRNA-21 promotes the cell proliferation, invasion and migration abilities in ovarian epithelial carcinomas through inhibiting the expression of PTEN protein. Int J Mol Med. 2010;26(6):819–27.

    Article  CAS  PubMed  Google Scholar 

  149. Chang H, Zhou X, Wang ZN, Song YX, Zhao F, Gao P, et al. Increased expression of miR-148b in ovarian carcinoma and its clinical significance. Mol Med Rep. 2012;5(5):1277–80.

    CAS  PubMed  Google Scholar 

  150. Zhang H, Zuo Z, Lu X, Wang L, Wang H, Zhu Z. MiR-25 regulates apoptosis by targeting Bim in human ovarian cancer. Oncol Rep. 2012;27(2):594–8.

    CAS  PubMed  Google Scholar 

  151. Wang X, Meng X, Li H, Liu W, Shen S, Gao Z. MicroRNA-25 expression level is an independent prognostic factor in epithelial ovarian cancer. Clin Transl Oncol. 2014;16(11):954–8.

    Article  CAS  PubMed  Google Scholar 

  152. Feng S, Pan W, Jin Y, Zheng J. MiR-25 promotes ovarian cancer proliferation and motility by targeting LATS2. Tumor Biol. 2014;35(12):12339–44.

    Article  CAS  Google Scholar 

  153. Langhe R, Norris L, Saadeh FA, Blackshields G, Varley R, Harrison A, et al. A novel serum microRNA panel to discriminate benign from malignant ovarian disease. Cancer Lett. 2015;356(2 Pt B):628–36.

    Article  CAS  PubMed  Google Scholar 

  154. Chan JK, Kiet TK, Blansit K, Ramasubbaiah R, Hilton JF, Kapp DS, et al. MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer. Gynecol Oncol. 2014;133(3):568–74.

    Article  CAS  PubMed  Google Scholar 

  155. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105(30):10513–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997–1006.

    Article  CAS  PubMed  Google Scholar 

  157. Chim SS, Shing TK, Hung EC, Leung TY, Lau TK, Chiu RW, et al. Detection and characterization of placental microRNAs in maternal plasma. Clin Chem. 2008;54(3):482–90.

    Article  CAS  PubMed  Google Scholar 

  158. Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, et al. Serum microRNAs are promising novel biomarkers. PLoS One. 2008;3(9), e3148.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  159. Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, et al. Detection of elevated levels of tumor-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141(5):672–5.

    Article  PubMed  Google Scholar 

  160. Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 2008;110(1):13–21.

    Article  CAS  PubMed  Google Scholar 

  161. Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS One. 2008;3(11), e3694.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  162. Cheng HH, Mitchell PS, Kroh EM, Dowell AE, Chery L, Siddiqui J, et al. Circulating microRNA profiling identifies a subset of metastatic prostate cancer patients with evidence of cancer-associated hypoxia. PLoS One. 2013;8(7), e69239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Resnick TD, McCulloch KA, Rougvie AE. miRNAs give worms the time of their lives: small RNAs and temporal control in Caenorhabditis elegans. Dev Dyn. 2010;239(5):1477–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Xu YZ, Xi QH, Ge WL, Zhang XQ. Identification of serum MicroRNA-21 as a biomarker for early detection and prognosis in human epithelial ovarian cancer. Asian Pac J Cancer Prev. 2013;14(2):1057–60.

    Article  PubMed  Google Scholar 

  165. Hong F, Li Y, Xu Y, Zhu L. Prognostic significance of serum microRNA-221 expression in human epithelial ovarian cancer. J Int Med Res. 2013;41(1):64–71.

    Article  CAS  PubMed  Google Scholar 

  166. Jiang H, Qu L, Wang Y, Cong J, Wang W, Yang X. miR-99a promotes proliferation targeting FGFR3 in human epithelial ovarian cancer cells. Biomed Pharmacother. 2014;68(2):163–9.

    Article  CAS  PubMed  Google Scholar 

  167. Liang H, Jiang Z, Xie G, Lu Y. Serum microRNA-145 as a novel biomarker in human ovarian cancer. Tumor Biol. 2015;36(7):5305–13.

    Article  CAS  Google Scholar 

  168. Gao YC, Wu J. MicroRNA-200c and microRNA-141 as potential diagnostic and prognostic biomarkers for ovarian cancer. Tumor Biol. 2015;36(6):4843–50.

    Article  CAS  Google Scholar 

  169. Ayaz L, Cayan F, Balci S, Gorur A, Akbayir S, Yildirim Yaroglu H, et al. Circulating microRNA expression profiles in ovarian cancer. J Obstet Gynaecol. 2014;34(7):620–4.

    Article  CAS  PubMed  Google Scholar 

  170. Shapira I, Oswald M, Lovecchio J, Khalili H, Menzin A, Whyte J, et al. Circulating biomarkers for detection of ovarian cancer and predicting cancer outcomes. Br J Cancer. 2014;110(4):976–83.

    Article  CAS  PubMed  Google Scholar 

  171. Zheng H, Zhang L, Zhao Y, Yang D, Song F, Wen Y, et al. Plasma miRNAs as diagnostic and prognostic biomarkers for ovarian cancer. PLoS One. 2013;8(11), e77853.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Shen W, Song M, Liu J, Qiu G, Li T, Hu Y, et al. MiR-26a promotes ovarian cancer proliferation and tumorigenesis. PLoS One. 2014;9(1), e86871.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  173. Hausler SF, Keller A, Chandran PA, Ziegler K, Zipp K, Heuer S, et al. Whole blood-derived miRNA profiles as potential new tools for ovarian cancer screening. Br J Cancer. 2010;103(5):693–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Masyuk AI, Masyuk TV, Larusso NF. Exosomes in the pathogenesis, diagnostics and therapeutics of liver diseases. J Hepatol. 2013;59(3):621–5.

    Article  CAS  PubMed  Google Scholar 

  175. Iero M, Valenti R, Huber V, Filipazzi P, Parmiani G, Fais S, et al. Tumor-released exosomes and their implications in cancer immunity. Cell Death Differ. 2008;15(1):80–8.

    Article  CAS  PubMed  Google Scholar 

  176. Simpson RJ, Lim JW, Moritz RL, Mathivanan S. Exosomes: proteomic insights and diagnostic potential. Expert Rev Proteomics. 2009;6(3):267–83.

    Article  CAS  PubMed  Google Scholar 

  177. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–9.

    Article  CAS  PubMed  Google Scholar 

  178. Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, Guha A, et al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumor cells. Nat Cell Biol. 2008;10(5):619–24.

    Article  CAS  PubMed  Google Scholar 

  179. Stoorvogel W, Kleijmeer MJ, Geuze HJ, Raposo G. The biogenesis and functions of exosomes. Traffic. 2002;3(5):321–30.

    Article  CAS  PubMed  Google Scholar 

  180. Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2(8):569–79.

    CAS  PubMed  Google Scholar 

  181. Al-Nedawi K, Meehan B, Rak J. Microvesicles: messengers and mediators of tumor progression. Cell Cycle. 2009;8(13):2014–8.

    Article  CAS  PubMed  Google Scholar 

  182. Keller S, Rupp C, Stoeck A, Runz S, Fogel M, Lugert S, et al. CD24 is a marker of exosomes secreted into urine and amniotic fluid. Kidney Int. 2007;72(9):1095–102.

    Article  CAS  PubMed  Google Scholar 

  183. Li QL, Bu N, Yu YC, Hua W, Xin XY. Exvivo experiments of human ovarian cancer ascites-derived exosomes presented by dendritic cells derived from umbilical cord blood for immunotherapy treatment. Clin Med Oncol. 2008;2:461–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  184. Runz S, Keller S, Rupp C, Stoeck A, Issa Y, Koensgen D, et al. Malignant ascites-derived exosomes of ovarian carcinoma patients contain CD24 and EpCAM. Gynecol Oncol. 2007;107(3):563–71.

    Article  CAS  PubMed  Google Scholar 

  185. Keller S, Konig AK, Marme F, Runz S, Wolterink S, Koensgen D, et al. Systemic presence and tumor-growth promoting effect of ovarian carcinoma released exosomes. Cancer Lett. 2009;278(1):73–81.

    Article  CAS  PubMed  Google Scholar 

  186. Cho JA, Yeo DJ, Son HY, Kim HW, Jung DS, Ko JK, et al. Exosomes: a new delivery system for tumor antigens in cancer immunotherapy. Int J Cancer. 2005;114(4):613–22.

    Article  PubMed  Google Scholar 

  187. Hegmans JP, Bard MP, Hemmes A, Luider TM, Kleijmeer MJ, Prins JB, et al. Proteomic analysis of exosomes secreted by human mesothelioma cells. Am J Pathol. 2004;164(5):1807–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Liang B, Peng P, Chen S, Li L, Zhang M, Cao D, et al. Characterization and proteomic analysis of ovarian cancer-derived exosomes. J Proteomics. 2013;80:171–82.

    Article  CAS  PubMed  Google Scholar 

  189. Taylor DD, Gercel-Taylor C. Tumor-derived exosomes and their role in cancer-associated T-cell signalling defects. Br J Cancer. 2005;92(2):305–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  190. Peng P, Yan Y, Keng S. Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity. Oncol Rep. 2011;25(3):749–62.

    CAS  PubMed  Google Scholar 

  191. Taylor DD, Gercel-Taylor C. The origin, function, and diagnostic potential of RNA within extracellular vesicles present in human biological fluids. Front Genet. 2013;4:142.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  192. Beach A, Zhang HG, Ratajczak MZ, Kakar SS. Exosomes: an overview of biogenesis, composition and role in ovarian cancer. J Ovarian Res. 2014;7(1):14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  193. Shih KK, Levine DA. Exosomal microRNAs step into the biomarker arena. Gynecol Oncol. 2008;110(1):1–2.

    Article  CAS  PubMed  Google Scholar 

  194. Chan JK, Blansit K, Kiet T, Sherman A, Wong G, Earle C, et al. The inhibition of miR-21 promotes apoptosis and chemosensitivity in ovarian cancer. Gynecol Oncol. 2014;132(3):739–44.

    Article  CAS  PubMed  Google Scholar 

  195. Frederick PJ, Green HN, Huang JS, Egger ME, Frieboes HB, Grizzle WE, et al. Chemoresistance in ovarian cancer linked to expression of microRNAs. Biotech Histochem. 2013;88(7):403–9.

    Article  CAS  PubMed  Google Scholar 

  196. Yu PN, Yan MD, Lai HC, Huang RL, Chou YC, Lin WC, et al. Downregulation of miR-29 contributes to cisplatin resistance of ovarian cancer cells. Int J Cancer. 2014;134(3):542–51.

    Article  CAS  PubMed  Google Scholar 

  197. Chen R, Alvero AB, Silasi DA, Kelly MG, Fest S, Visintin I, et al. Regulation of IKKbeta by miR-199a affects NF-kappaB activity in ovarian cancer cells. Oncogene. 2008;27(34):4712–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Testa JR, Bellacosa A. AKT plays a central role in tumorigenesis. Proc Natl Acad Sci U S A. 2001;98(20):10983–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Kamazawa S, Kigawa J, Kanamori Y, Itamochi H, Sato S, Iba T, et al. Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based chemotherapy for patients with ovarian cancer. Gynecol Oncol. 2002;86(2):171–6.

    Article  CAS  PubMed  Google Scholar 

  200. Penson RT, Oliva E, Skates SJ, Glyptis T, Fuller Jr AF, Goodman A, et al. Expression of multidrug resistance-1 protein inversely correlates with paclitaxel response and survival in ovarian cancer patients: a study in serial samples. Gynecol Oncol. 2004;93(1):98–106.

    Article  CAS  PubMed  Google Scholar 

  201. Zhu H, Wu H, Liu X, Evans BR, Medina DJ, Liu CG, et al. Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem Pharmacol. 2008;76(5):582–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Yang LY, Wang HJ, Jia XB, Wang X, Luo J, Zhang XY. [Expression of miR-130a in cisplatin resistant cell lines of ovarian cancer]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2012;43(1):60–4.

    CAS  PubMed  Google Scholar 

  203. Zhou Y, Chen Q, Qin R, Zhang K, Li H. MicroRNA-449a reduces cell survival and enhances cisplatin-induced cytotoxicity via downregulation of NOTCH1 in ovarian cancer cells. Tumor Biol. 2014;35(12):12369–78.

    Article  CAS  Google Scholar 

  204. Li H, Xu H, Shen H, Li H. microRNA-106a modulates cisplatin sensitivity by targeting PDCD4 in human ovarian cancer cells. Oncol Lett. 2014;7(1):183–8.

    CAS  PubMed  Google Scholar 

  205. Huh JH, Kim TH, Kim K, Song JA, Jung YJ, Jeong JY, et al. Dysregulation of miR-106a and miR-591 confers paclitaxel resistance to ovarian cancer. Br J Cancer. 2013;109(2):452–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Kim YW, Kim EY, Jeon D, Liu JL, Kim HS, Choi JW, et al. Differential microRNA expression signatures and cell type-specific association with Taxol resistance in ovarian cancer cells. Drug Des Devel Ther. 2014;8:293–314.

    CAS  PubMed  PubMed Central  Google Scholar 

  207. Hong L, Yang Z, Ma J, Fan D. Function of miRNA in controlling drug resistance of human cancers. Curr Drug Targets. 2013;14(10):1118–27.

    Article  CAS  PubMed  Google Scholar 

  208. Ye G, Fu G, Cui S, Zhao S, Bernaudo S, Bai Y, et al. MicroRNA 376c enhances ovarian cancer cell survival by targeting activin receptor-like kinase 7: implications for chemoresistance. J Cell Sci. 2011;124(Pt 3):359–68.

    Article  CAS  PubMed  Google Scholar 

  209. Lu L, Schwartz P, Scarampi L, Rutherford T, Canuto EM, Yu H, et al. MicroRNA let-7a: a potential marker for selection of paclitaxel in ovarian cancer management. Gynecol Oncol. 2011;122(2):366–71.

    Article  CAS  PubMed  Google Scholar 

  210. Liu L, Zou J, Wang Q, Yin FQ, Zhang W, Li L. Novel microRNAs expression of patients with chemotherapy drug-resistant and chemotherapy-sensitive epithelial ovarian cancer. Tumor Biol. 2014;35(8):7713–7.

    Article  CAS  Google Scholar 

  211. Kong F, Sun C, Wang Z, Han L, Weng D, Lu Y, et al. miR-125b confers resistance of ovarian cancer cells to cisplatin by targeting pro-apoptotic Bcl-2 antagonist killer 1. J Huazhong Univ Sci Technolog Med Sci. 2011;31(4):543–9.

    Article  CAS  PubMed  Google Scholar 

  212. Li B, Chen H, Wu N, Zhang WJ, Shang LX. Deregulation of miR-128 in ovarian cancer promotes cisplatin resistance. Int J Gynecol Cancer. 2014;24(8):1381–8.

    Article  PubMed  Google Scholar 

  213. Zou D, Wang D, Li R, Tang Y, Yuan L, Long X, et al. MiR-197 induces Taxol resistance in human ovarian cancer cells by regulating NLK. Tumor Biology. 2015

    Google Scholar 

  214. Mitamura T, Watari H, Wang L, Kanno H, Hassan MK, Miyazaki M, et al. Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET. Oncogenesis. 2013;2, e40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Creighton CJ, Fountain MD, Yu Z, Nagaraja AK, Zhu H, Khan M, et al. Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers. Cancer Res. 2010;70(5):1906–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Vecchione A, Belletti B, Lovat F, Volinia S, Chiappetta G, Giglio S, et al. A microRNA signature defines chemoresistance in ovarian cancer through modulation of angiogenesis. Proc Natl Acad Sci U S A. 2013;110(24):9845–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St. James’s Hospital, Dublin, Ireland

    Ream Langhe

Authors
  1. Ream Langhe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ream Langhe .

Editor information

Editors and Affiliations

  1. Department of Physiology, Columbia University Medical Center, New York, New York, USA

    Gaetano Santulli

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Langhe, R. (2015). microRNA and Ovarian Cancer. In: Santulli, G. (eds) microRNA: Cancer. Advances in Experimental Medicine and Biology, vol 889. Springer, Cham. https://doi.org/10.1007/978-3-319-23730-5_8

Download citation

Publish with us

Policies and ethics

Search

Navigation