DOI: https://doi.org/None

E.S. Gershtein (1,3), D.N. Kushlinsky (1,3), L.V. Adamyan (2,3), N.E. Kushlinskii (1,3) 1 -N.N. Blokhin Cancer Research Center, Kashirskoye shosse, 24, Moscow, 115478, Russian Federation; 2 -Academician V.I. Kulakov Research Center for Obstetrics and Gynecology and Perinatology, Akademika Oparina str., 4, Moscow, 117997, Russian Federation; 3 -A.I. Evdokimov Moscow State University of Medicine and Dentistry, Delegatskaya str., 20, Moscow, 127473, Russian Federation

MicroRNAs (miRNAs) – small non-coding RNAs targeting multiple mRNAs – are posttranscriptional regulators of gene expression involved in carcinogenesis, metastasis, and invasion. MiRNAs expression is altered in various human tumors including ovarian cancer. Analysis of published data describing the pattern of miRNAs expression and its changes in ovarian cancer tissue and in peripheral blood with the accent on the possibility of their application as diagnostic, prognostic, and predictive biomarkers in this diseaseis presented. Results of the most valuable published clinical laboratory studies found in PubMed database in the period from 2007 to 2016 are summarized and critically evaluated. Expression of several tens of miRNAs was shown to be both up- and downregulated in ovarian cancer compared to normal ovarian tissues. Similar changes were revealed in peripheral blood of ovarian cancer patients as compared to healthy persons. Substantial number of evidence indicating to good prospects of miRNAs application both in diagnostics, including non-invasive serological approach, and in general prognosis and, more important, in prediction of resistance to standard chemotherapy (platinum derivatives, taxans) has been accumulated. However, the diversity and inconsistence of these data prevent marking out of accurate and reliable candidates for clinically valuable biomarkers at the present stage. MicroRNAs are promising biological markers for ovarian cancer, but further data accumulation, unification of methods and results’ evaluation criteria are needed for successive practical application of miRNA based tests.
microRNA, ovarian cancer, regulation, diagnostics, prognosis

Список литературы: 
  1. Melo C.A., Melo S.A. MicroRNA biogen-esis: dicing assay. Methods Mol. Biol. 2014; 1182: 219–26.
  2. Sun D., Layer R., Mueller A.C., Cichewicz M.A., Negishi M., Paschal B.M., Dutta A. Regulation of several androgen-induced genes through the repression of the miR-99a/let-7c/miR-125b-2 miRNA cluster in prostate cancer cells. Oncogene. 2014; 33 (11): 1448–57.
  3. Hayes J., Peruzzi P.P., Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol. Med. 2014; 20 (8): 460–9.
  4. Kozomara A., Griffiths-Jones S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 2014; 42: 68–73.
  5. Nowee M.E., Snijders A.M., Rockx D.A., de Wit R.M., Kosma V.M., Hamalainen K., Schouten J.P., Verheijen R.H., van Diest P.J., Albertson D.G. et al. DNA profiling of primary serous ovarian and fallopian tube carcinomas with array compara-tive genomic hybridization and multiplex ligation-dependent probe amplification. J. Pathol. 2007; 213 (1): 46–55.
  6. Iorio M.V., Visone R., Di Leva G., Donati V., Petrocca F., Casalini P., Taccioli C., Volinia S., Liu C.G., Alder H. et al. MicroRNA signatures in human ovarian cancer. Cancer Res. 2007; 67 (18): 8699–707.
  7. Chen Y., Zhang L., Hao Q. Candidate microRNA biomarkers in human epithelial ovarian cancer: systematic review profil-ing studies and experimental validation. Cancer Cell. Int. 2013; 13 (1): 86.
  8. Kim T.H., Kim Y.K., Kwon Y., Heo J.H., Kang H., Kim G., An H.J. Deregulation of miR-519a, 153, and 485-5p and its clinicopathological relevance in ovarian epithelial tumours. Histopathology. 2010; 57 (5): 734–43
  9. Zhang L., Volinia S., Bonome T., Calin G.A., Greshock J., Yang N., Liu C.G., Gian-nakakis A., Alexiou P., Hasegawa K. et al. Genomic and epigenetic alterations deregulate microRNA expression in hu-man epithelial ovarian cancer. Proc Natl Acad Sci USA. 2008; 105 (19): 7004–9.
  10. Nam E.J., Yoon H., Kim S.W., Kim H., Kim Y.T., Kim J.H., Kim J.W., Kim S. MicroRNA expression profiles in serous ovarian car-cinoma. Clin. Cancer Res. 2008; 14 (9): 2690–5.
  11. Dahiya N., Sherman-Baust C.A., Wang T.L., Davidson B., Shih Ie. M., Zhang Y., Wood W., 3rd, Becker K.G., Morin P.J. MicroRNA expression and identification of putative miRNA targets in ovarian cancer. PLoS One. 2008; 3 (6): 2436.
  12. Yang N., Kaur S., Volinia S., Greshock J., Lassus H., Hasegawa K., Liang S., Leminen A., Deng S., Smith L. 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.
  13. Wyman S.K., Parkin R.K., Mitchell P.S., Fritz B.R., O’Briant K., Godwin A.K., Urban N., Drescher C.W., Knudsen B.S., Tewari M. Repertoire of microRNAs in epithelial ovarian cancer as determined by next generation sequencing of small RNA cDNA libraries. PLoS One. 2009; 4 (4): 5311.
  14. Chao A., Lin C.Y., Lee Y.S., Tsai C.L., Wei P.C., Hsueh S., Wu T.I., Tsai C.N., Wang C.J., Chao A.S. et al. Regulation of ovar-ian cancer progression by microRNA-187 through targeting Disabled homolog-2. Oncogene. 2012; 31 (6): 764–75.
  15. Iorio M.V., Croce C.M. MicroRNA profiling in ovarian cancer. Methods Mol. Biol. 2013; 1049: 187–97.
  16. Yang L., Li N., Wang H., Jia X., Wang X., Luo J. Altered microRNA expression in cisplatin-resistant ovarian cancer cells and upregulation of miR-130a associated with MDR1/P-glycoprotein-mediated drug re-sistance. Oncol. Rep. 2012; 28 (2): 592–600.
  17. Yang H., Kong W., He L., Zhao J.J., O’Donnell J.D., Wang J., Wenham R.M., Coppola D., Kruk P.A., Nicosia S.V. et al. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell sur-vival and cisplatin resistance by targeting PTEN. Cancer Res. 2008; 68 (2): 425–33.
  18. Ling S., Ruiqin M., Guohong Z., Ying W. Expression and prognostic significance of microRNA-451 in human epithelial ovar-ian cancer. Eur J. Gynaecol. Oncol. 2015; 36 (4): 463–8.
  19. Yu X., Zhang X., Bi T., Ding Y., Zhao J., Wang C., Jia T., Han D., Guo G., Wang B. et al. MiRNA expression signature for potentially predicting the prognosis of ovarian serous carcinoma. Tumour Biol. 2013; 34 (6): 3501–8.
  20. Liu M., Zhang X., Hu C.F., Xu Q., Zhu H.X., Xu N.Z. MicroRNA-mRNA functional pairs for cisplatin resistance in ovarian cancer cells. Chin J. Cancer. 2014; 33 (6): 285–94.
  21. Liu Z., Gersbach E., Zhang X., Xu X., Dong R., Lee P., Liu J., Kong B., Shao C., Wei J.J. miR-106a represses the Rb tumor suppres-sor p130 to regulate cellular proliferation and differentiation in high-grade serous ovarian carcinoma. Mol. Cancer Res. 2013; 11 (11): 1314–25.
  22. Wang X., Meng X., Li H., Liu W., Shen S., Gao Z. MicroRNA-25 expression level is an independent prognostic factor in epi-thelial ovarian cancer. Clin. Transl Oncol. 2014; 16 (11): 954–8.
  23. Wang L., Zhu M.J., Ren A.M., Wu H.F., Han W.M., Tan R.Y., Tu R.Q. A ten-microRNA signature identified from a genome-wide microRNA expression profiling in human epithelial ovarian cancer. PLoS One. 2014; 9 (5): 96472.
  24. Wang S., Zhao X., Wang J., Wen Y., Zhang L., Wang D., Chen H., Chen Q., Xiang W. Upregulation of microRNA-203 is associ-ated with advanced tumor progression and poor prognosis in epithelial ovarian cancer. Med. Oncol. 2013; 30 (3): 681.
  25. Fan Y., Fan J., Huang L., Ye M., Huang Z., Wang Y., Li Q., Huang J. Increased expres-sion of microRNA-196a predicts poor prognosis in human ovarian carcinoma. Int J. Clin. Exp. Pathol. 2015; 8 (4): 4132–7.
  26. Jin M., Yang Z., Ye W., Xu H., Hua X. Micro-RNA-150 predicts a favorable prognosis in patients with epithelial ovarian cancer, and inhibits cell invasion and metastasis by suppressing transcriptional repressor ZEB1. PLoS One. 2014; 9 (8): 103965.
  27. Kim Y.W., Kim E.Y., Jeon D., Liu J.L., Kim H.S., Choi J.W., Ahn W.S. Differential microRNA expression signatures and cell type-specific association with Taxol resist-ance in ovarian cancer cells. Drug Des Devel Ther. 2014; 8: 293–314.
  28. Vilming Elgaaen B., Olstad O.K., Haug K.B., Brusletto B., Sandvik L., Staff A.C., Gautvik K.M., Davidson B. Global miRNA expression analysis of serous and clear cell ovarian carcinomas identifies dif-ferentially expressed miRNAs including miR-200c-3p as a prognostic marker. BMC Cancer. 2014; 14: 80.
  29. Tang Z., Ow G.S., Thiery J.P., Ivshina A.V., Kuznetsov V.A. Meta-analysis of transcrip-tome reveals let-7b as an unfavorable prognostic biomarker and predicts molecular and clinical subclasses in high-grade serous ovarian carcinoma. Int J. Cancer. 2013; 134 (2): 306–18.
  30. Qin C.Z., Lou X.Y., Lv Q.L., Cheng L., Wu N.Y., Hu L., Zhou H.H. MicroRNA-184 acts as a potential diagnostic and prognostic marker in epithelial ovarian cancer and regulates cell proliferation, apoptosis and inflammation. Pharmazie. 2015; 70 (10): 668–73.
  31. Li W., Liu Z., Chen L., Zhou L., Yao Y. Micro-RNA-23b is an independent prognostic marker and suppresses ovarian cancer progression by targeting runt-related transcription factor-2. FEBS Lett. 2014; 588 (9): 1608–15.
  32. Luo J., Zhou J., Cheng Q., Zhou C., Ding Z. Role of microRNA-133a in epithelial ovar-ian cancer pathogenesis and progres-sion. Oncol Lett. 2014; 7 (4): 1043–8
  33. Wang Y., Li L., Qu Z., Li R., Bi T., Jiang J., Zhao H. The expression of miR-30a* and miR-30e* is associated with a dualistic model for grading ovarian papillary seri-ous carcinoma. Int J. Oncol. 2014; 44 (6): 1904–14.
  34. Zhou J., Gong G., Tan H., Dai F., Zhu X., Chen Y., Wang J., Liu Y., Chen P., Wu X. et al. Urinary microRNA-30a-5p is a potential biomarker for ovarian serous adenocarci-noma. Oncol. Rep. 2015; 33 (6): 2915–23.
  35. Zhang X., Guo G., Wang G., Zhao J., Wang B., Yu X., Ding Y. Profile of differen-tially expressed miRNAs in high-grade serous carcinoma and clear cell ovarian carcinoma, and the expression of miR-510 in ovarian carcinoma. Mol. Med. Rep. 2015.
  36. Banno K., Yanokura M., Iida M., Adachi M., Nakamura K., Nogami Y., Umene K., Masuda K., Kisu I., Nomura H. et al. Ap-plication of microRNA in diagnosis and treatment of ovarian cancer. Biomed Res Int. 2014; 2014: 232817.
  37. Vecchione A., Belletti B., Lovat F., Volinia S., Chiappetta G., Giglio S., Sonego M., Cirombella R., Onesti E.C., Pellegrini P. et al. A microRNA signature defines chem-oresistance in ovarian cancer through modulation of angiogenesis. Proc Natl Acad Sci USA. 2013; 110 (24): 9845–50
  38. Ying H.C., Xu H.Y., Lv J., Ying T.S., Yang Q. MicroRNA signatures of platinum-resist-ance in ovarian cancer. Eur J. Gynaecol Oncol. 2015; 36 (1): 16–20.
  39. Brozovic A., Duran G.E., Wang Y.C., Francisco E.B., Sikic B.I. The miR-200 family differentially regulates sensitivity to pacli-taxel and carboplatin in human ovarian carcinoma OVCAR-3 and MES-OV cells. Mol. Oncol. 2015; 9 (8): 1678–93.
  40. Davidson B., Trope C.G., Reich R. The clinical and diagnostic role of microRNAs in ovarian carcinoma. Gynecol Oncol. 2014; 133 (3): 640–6.
  41. Langhe R. microRNA and Ovarian Can-cer. Adv Exp Med. Biol. 2015; 889: 119–51.
  42. Petrillo M., Zannoni G., Beltrame L., Mar-tinelli E., DiFeo A., Paracchini L., Craparot-ta I., Mannarino L., Vizzielli G., Scambia G. et al. Identification of high-grade serous ovarian cancer miRNA species associ-ated with survival and drug response in patients receiving neo-adjuvant chemo-therapy: a retrospective longitudinal analysis using matched tumor biopsies. Ann Oncol. 2016. doi: 10.1093/annonc/mdw007
  43. Cheng W., Liu T., Wan X., Gao Y., Wang H. MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resist-ance of ovarian cancer-initiating cells. FEBS J. 2012; 279 (11): 2047–59.
  44. Joshi H.P., Subramanian I.V., Schnettler E.K., Ghosh G., Rupaimoole R., Evans C., Saluja M., Jing Y., Cristina I., Roy S. et al. Dynamin 2 along with microRNA-199a reciprocally regulate hypoxia-inducible factors and ovarian cancer metastasis. Proc Natl Acad Sci USA. 2014; 111 (14): 5331–6.
  45. Kinose Y., Sawada K., Nakamura K., Sa-wada I., Toda A., Nakatsuka E., Hashim-oto K., Mabuchi S., Takahashi K., Kurachi H. et al. The hypoxia-related microRNA miR-199a-3p displays tumor suppressor functions in ovarian carcinoma. Onco-target. 2015; 6 (13): 11342–56.
  46. Liu M.X., Siu M.K., Liu S.S., Yam J.W., Ngan H.Y., Chan D.W. Epigenetic silencing of microRNA-199b-5p is associated with ac-quired chemoresistance via activation of JAG1-Notch1 signaling in ovarian cancer. Oncotarget. 2014; 5 (4): 944–58.
  47. Wang Z., Ting Z., Li Y., Chen G., Lu Y., Hao X. microRNA-199a is able to reverse cispl-atin resistance in human ovarian cancer cells through the inhibition of mammalian target of rapamycin. Oncol Lett. 2013; 6 (3): 789–94.
  48. Zhao H.M., Wei W., Sun Y.H., Gao J.H., Wang Q., Zheng J.H. MicroRNA-9 promotes tumorigenesis and mediates sensitivity to cisplatin in primary epithelial ovarian cancer cells. Tumour Biol. 2015; 36 (9): 6867–73.
  49. Guo L.M., Pu Y., Han Z., Liu T., Li Y.X., Liu M., Li X., Tang H. MicroRNA-9 inhibits ovarian cancer cell growth through regulation of NF-kappaB1. FEBS J. 2009; 276 (19): 5537–46.
  50. Zhao S.F., Zhang X., Zhang X.J., Shi X.Q., Yu Z.J., Kan Q.C. Induction of micro-RNA-9 mediates cytotoxicity of curcumin against SKOV3 ovarian cancer cells. Asian Pac J. Cancer Prev. 2014; 15 (8): 3363–8.
  51. Dong R., Liu X., Zhang Q., Jiang Z., Li Y., Wei Y., Yang Q., Liu J., Wei J.J., Shao C. et al. miR-145 inhibits tumor growth and metastasis by targeting metadherin in high-grade serous ovarian carcinoma. Oncotarget. 2014; 5 (21): 10816–29.
  52. 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. 2013; 13 (2): 161–8.
  53. Zhou J., Gong J., Ding C., Chen G. Quer-cetin induces the apoptosis of human ovarian carcinoma cells by upregulating the expression of microRNA-145. Mol. Med. Rep. 2015; 12 (2): 3127–31.
  54. Nagaraja A.K., Creighton C.J., Yu Z., Zhu H., Gunaratne P.H., Reid J.G., Olokpa E., Itamochi H., Ueno N.T., Hawkins S.M. et al. A link between mir-100 and FRAP1/mTOR in clear cell ovarian cancer. Mol. Endocrinol. 2010; 24 (2): 447–63.
  55. Peng D.X., Luo M., Qiu L.W., He Y.L., Wang X.F. Prognostic implications of micro-RNA-100 and its functional roles in human epithelial ovarian cancer. Oncol. Rep. 2012; 27 (4): 1238–44.
  56. Chen P., Zeng M., Zhao Y., Fang X. Upregu-lation of Limk1 caused by microRNA-138 loss aggravates the metastasis of ovarian cancer by activation of Limk1/cofilin sign-aling. Oncol. Rep. 2014; 32 (5): 2070–6.
  57. Yeh Y.M., Chuang C.M., Chao K.C., Wang L.H. MicroRNA-138 suppresses ovarian cancer cell invasion and metastasis by targeting SOX4 and HIF-1alpha. Int J. Cancer. 2013; 133 (4): 867–78.
  58. Fu X., Tian J., Zhang L., Chen Y., Hao Q. Involvement of microRNA-93, a new regulator of PTEN/Akt signaling pathway, in regulation of chemotherapeutic drug cisplatin chemosensitivity in ovarian can-cer cells. FEBS Lett. 2012; 586 (9): 1279–86.
  59. Chen X., Chen S., Xiu Y.L., Sun K.X., Zong Z.H., Zhao Y. RhoC is a major target of microRNA-93-5P in epithelial ovarian car-cinoma tumorigenesis and progression. Mol. Cancer. 2015; 14: 31.
  60. Wang W., Ren F., Wu Q., Jiang D., Li H., Peng Z., Wang J., Shi H. MicroRNA-497 inhibition of ovarian cancer cell migration and invasion through targeting of SMAD specific E3 ubiquitin protein ligase 1. Biochem Biophys Res Commun. 2014; 449 (4): 432–7.
  61. Wang W., Ren F., Wu Q., Jiang D., Li H., Shi H. MicroRNA-497 suppresses angiogen-esis 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.
  62. Chen S., Jiao J.W., Sun K.X., Zong Z.H., Zhao Y. MicroRNA-133b targets glu-tathione S-transferase pi expression to increase ovarian cancer cell sensitivity to chemotherapy drugs. Drug Des Devel Ther. 2015; 9: 5225–35.
  63. Chen S., Chen X., Xiu Y.L., Sun K.X., Zong Z.H., Zhao Y. microRNA 490-3P enhances the drug-resistance of human ovarian cancer cells. J. Ovarian Res. 2014; 7: 84.
  64. Chen S., Chen X., Xiu Y.L., Sun K.X., Zhao Y. MicroRNA-490-3P targets CDK1 and inhibits ovarian epithelial carcinoma tumorigenesis and progression. Cancer Lett. 2015; 362 (1): 122–30.
  65. Zhao S., Wen Z., Liu S., Liu Y., Li X., Ge Y., Li S. MicroRNA-148a inhibits the proliferation and promotes the paclitaxel-induced apoptosis of ovarian cancer cells by targeting PDIA3. Mol. Med. Rep. 2015; 12 (3): 3923–9.
  66. Wen Z., Zhao S., Liu S., Liu Y., Li X., Li S. MicroRNA-148a inhibits migration and in-vasion of ovarian cancer cells via target-ing sphingosine-1-phosphate receptor 1. Mol. Med. Rep. 2015; 12 (3): 3775–80.
  67. Xie Y.L., Yang Y.J., Tang C., Sheng H.J., Jiang Y., Han K., Ding L.J. Estrogen com-bined with progesterone decreases cell proliferation and inhibits the expression of Bcl-2 via microRNA let-7a and miR-34b in ovarian cancer cells. Clin. Transl Oncol. 2014; 16 (10): 898–905.
  68. Corney D.C., Flesken-Nikitin A., Godwin A.K., Wang W., Nikitin A.Y. MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell prolifera-tion and adhesion-independent growth. Cancer Res. 2007; 67 (18): 8433–8.
  69. Guo F., Cogdell D., Hu L., Yang D., Sood A.K., Xue F., Zhang W. MiR-101 suppresses the epithelial-to-mesenchymal transition by targeting ZEB1 and ZEB2 in ovarian carcinoma. Oncol. Rep. 2014; 31 (5): 2021–8.
  70. Semaan A., Qazi A.M., Seward S., Chamala S., Bryant C.S., Kumar S., Morris R., Steffes C.P., Bouwman D.L., Munkarah A.R. et al. MicroRNA-101 inhibits growth of epithelial ovarian cancer by reliev-ing chromatin-mediated transcriptional repression of p21(waf(1)/cip(1)). Pharm Res. 2011; 28 (12): 3079–90.
  71. Jia W., Eneh J.O., Ratnaparkhe S., Alt-man M.K., Murph M.M. MicroRNA-30c-2* expressed in ovarian cancer cells sup-presses growth factor-induced cellular proliferation and downregulates the oncogene BCL9. Mol. Cancer Res. 2011; 9 (12): 1732–45.
  72. Abdelmohsen K., Srikantan S., Kuwano Y., Gorospe M. miR-519 reduces cell prolif-eration by lowering RNA-binding protein HuR levels. Proc Natl Acad Sci USA. 2008; 105 (51): 20297–302.
  73. Imam J.S., Buddavarapu K., Lee-Chang J.S., Ganapathy S., Camosy C., Chen Y., Rao M.K. MicroRNA-185 suppresses tumor growth and progression by targeting the Six1 oncogene in human cancers. Onco-gene. 2010; 29 (35): 4971–9.
  74. 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.
  75. Zhou X., Hu Y., Dai L., Wang Y., Zhou J., Wang W., Di W., Qiu L. 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): 96718.
  76. Dai F., Zhang Y., Zhu X., Shan N., Chen Y. Anticancer role of MUC1 aptamer-miR-29b chimera in epithelial ovarian carcinoma cells through regulation of PTEN methylation. Target Oncol. 2012; 7 (4): 217–25.
  77. Shahab S.W., Matyunina L.V., Hill C.G., Wang L., Mezencev R., Walker L.D., McDonald J.F. The effects of MicroRNA transfections on global patterns of gene expression in ovarian cancer cells are functionally coordinated. BMC Med. Genomics. 2012; 5: 33.
  78. 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.
  79. Nakano H., Yamada Y., Miyazawa T., Yoshida T. Gain-of-function microRNA screens identify miR-193a regulating proliferation and apoptosis in epithelial ovarian cancer cells. Int J. Oncol. 2013; 42 (6): 1875–82.
  80. Denoyelle C., Lambert B., Meryet-Figuiere M., Vigneron N., Brotin E., Lecerf C., Abei-lard E., Giffard F., Louis M.H., Gauduchon P. et al. miR-491-5p-induced apoptosis in ovarian carcinoma depends on the direct inhibition of both BCL-XL and EGFR leading to BIM activation. Cell Death Dis. 2014; 5: 1445.
  81. 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. Tumour Biol. 2014; 35 (12): 12369–78.
  82. Liu T., Hou L., Huang Y. EZH2-specific mi-croRNA-98 inhibits human ovarian cancer stem cell proliferation via regulating the pRb-E2F pathway. Tumour Biol. 2014; 35 (7): 7239–47.
  83. Li S., Li Y., Wen Z., Kong F., Guan X., Liu W. microRNA-206 overexpression inhibits cellular proliferation and invasion of estrogen receptor alpha-positive ovarian cancer cells. Mol. Med. Rep. 2014; 9 (5): 1703–8.
  84. Chen X.P., Chen Y.G., Lan J.Y., Shen Z.J. MicroRNA-370 suppresses proliferation and promotes endometrioid ovarian cancer chemosensitivity to cDDP by negatively regulating ENG. Cancer Lett. 2014; 353 (2): 201–10.
  85. Wen C., Liu X., Ma H., Zhang W., Li H. miR3383p suppresses tumor growth of ovarian epithelial carcinoma by target-ing Runx2. Int J. Oncol. 2015; 46 (5): 2277–85
  86. Tian X., Xu L., Wang P. MiR-191 inhibits TNF-alpha induced apoptosis of ovarian endometriosis and endometrioid carci-noma cells by targeting DAPK1. Int J. Clin. Exp. Pathol. 2015; 8 (5): 4933–42.
  87. Zhou J., Xie M., Shi Y., Luo B., Gong G., Li J., Wang J., Zhao W., Zi Y., Wu X. et al. MicroRNA-153 functions as a tumor suppressor by targeting SET7 and ZEB2 in ovarian cancer cells. Oncol. Rep. 2015; 34 (1): 111–20.
  88. Zhang L., Li Z., Gai F., Wang Y. Micro-RNA-137 suppresses tumor growth in epithelial ovarian cancer in vitro and in vivo. Mol. Med. Rep. 2015; 12 (2): 3107–14.
  89. Tan G., Cao X., Dai Q., Zhang B., Huang J., Xiong S., Zhang Y., Chen W., Yang J., Li H. A novel role for microRNA-129-5p in inhibiting ovarian cancer cell prolifera-tion and survival via direct suppression of transcriptional co-activators YAP and TAZ. Oncotarget. 2015; 6 (11): 8676–86.
  90. Luo P., Fei J., Zhou J., Zhang W. micro-RNA-126 suppresses PAK4 expression in ovarian cancer SKOV3 cells. Oncol Lett. 2015; 9 (5): 2225–9.
  91. Lin K.T., Yeh Y.M., Chuang C.M., Yang S.Y., Chang J.W., Sun S.P., Wang Y.S., Chao K.C., Wang L.H. Glucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer metastasis through targeting Rap1B. Nat Commun. 2015; 6: 5917.
  92. Ge T., Yin M., Yang M., Liu T., Lou G. Micro-RNA-302b suppresses human epithelial ovarian cancer cell growth by targeting RUNX1. Cell Physiol. Biochem. 2015; 34 (6): 2209–20.
  93. Ibrahim F.F., Jamal R., Syafruddin S.E., Ab Mutalib N.S., Saidin S., MdZin R.R., Hossain Mollah M.M., Mokhtar N.M. MicroRNA-200c and microRNA-31 regulate proliferation, colony formation, migration and invasion in serous ovarian cancer. J. Ovarian Res. 2015; 8: 56.
  94. Chen S., Chen X., Xiu Y.L., Sun K.X., Zhao Y. Inhibition of Ovarian Epithelial Carci-noma Tumorigenesis and Progression by microRNA 106b Mediated through the RhoC Pathway. PLoS One. 2015; 10 (5): 0125714.
  95. Jabbari N., Reavis A.N., McDonald J.F. Sequence variation among members of the miR-200 microRNA family is correlated with variation in the ability to induce hallmarks of mesenchymal-epithelial transition in ovarian cancer cells. J. Ovar-ian Res. 2014; 7: 12.
  96. Chen D., Zhang Y., Wang J., Chen J., Yang C., Cai K., Wang X., Shi F., Dou J. MicroRNA-200c overexpression inhib-its tumorigenicity and metastasis of CD117+CD44+ ovarian cancer stem cells by regulating epithelial-mesenchymal transition. J. Ovarian Res. 2013; 6 (1): 50.
  97. Gao N., Tian J.X., Shang Y.H., Zhao D.Y., Wu T. Catalpol suppresses proliferation and facilitates apoptosis of OVCAR-3 ovarian cancer cells through upregulat-ing microRNA-200 and downregulating MMP-2 expression. Int J. Mol. Sci. 2014; 15 (11): 19394–405.
  98. Koutsaki M., Spandidos D.A., Zaravinos A. Epithelial-mesenchymal transition-associ-ated miRNAs in ovarian carcinoma, with highlight on the miR-200 family: prognos-tic value and prospective role in ovarian cancer therapeutics. Cancer Lett. 2014; 351 (2): 173–81.
  99. Knouf E.C., Garg K., Arroyo J.D., Correa Y., Sarkar D., Parkin R.K., Wurz K., O’Briant K.C., Godwin A.K., Urban N.D. et al. An integrative genomic approach identifies p73 and p63 as activators of miR-200 microRNA family transcription. Nucleic Acids Res. 2011; 40 (2): 499–510.
  100. Liu N., Zhong L., Zeng J., Zhang X., Yang Q., Liao D., Wang Y., Chen G. Upregula-tion of microRNA-200a associates with tumor proliferation, CSCs phenotype and chemosensitivity in ovarian cancer. Neoplasma. 2015; 62 (4): 550–9.
  101. Nam E.J., Lee M., Yim G.W., Kim J.H., Kim S., Kim S.W., Kim Y.T. MicroRNA profiling of a CD133(+) spheroid-forming subpopu-lation of the OVCAR3 human ovarian cancer cell line. BMC Med. Genomics. 2012; 5: 18.
  102. Wu Q., Guo R., Lin M., Zhou B., Wang Y. MicroRNA-200a inhibits CD133/1+ ovarian cancer stem cells migration and invasion by targeting E-cadherin repressor ZEB2. Gynecol. Oncol. 2011; 122 (1): 149–54.
  103. Gao Y., Meng H., Liu S., Hu J., Zhang Y., Jiao T., Liu Y., Ou J., Wang D., Yao L. et al. LncRNA-HOST2 regulates cell biological behaviors in epithelial ovarian cancer through a mechanism involving micro-RNA let-7b. Hum Mol. Genet. 2014; 24 (3): 841–52.
  104. Liu N., Zhou C., Zhao J., Chen Y. Reversal of paclitaxel resistance in epithelial ovar-ian carcinoma cells by a MUC1 aptamer-let-7i chimera. Cancer Invest. 2012; 30 (8): 577–82.
  105. Su Z., Hou X.K., Wen Q.P. Propofol induces apoptosis of epithelial ovarian cancer cells by upregulation of microRNA let-7i expression. Eur J. Gynaecol. Oncol. 2015; 35 (6): 688–91.
  106. Xu C.X., Xu M., Tan L., Yang H., Permuth-Wey J., Kruk P.A., Wenham R.M., Nicosia S.V., Lancaster J.M., Sellers T.A. et al. MicroRNA miR-214 regulates ovarian cancer cell stemness by targeting p53/Nanog. J. Biol. Chem. 2012; 287 (42): 34970–8.
  107. Chen Y.F., Dong Z., Xia Y., Tang J., Peng L., Wang S., Lai D. Nucleoside analog inhibits microRNA-214 through targeting heat-shock factor 1 in human epithelial ovarian cancer. Cancer Sci. 2013; 104 (12): 1683–9.
  108. Zong C., Wang J., Shi T.M. MicroRNA 130b enhances drug resistance in human ovar-ian cancer cells. Tumour Biol. 2014; 35 (12): 12151–6.
  109. Li Z.M., Hu S., Xiao L., Wang J., Cai J., Yu L.L., Wang Z.H. [Expression of microRNA 27a and its correlation with drug resist-ance in human ovarian cancer A2780/Taxol cells]. Zhonghua Fu Chan Ke Za Zhi. 2010; 45 (5): 372–5.
  110. Xu L., Xiang J., Shen J., Zou X., Zhai S., Yin Y., Li P., Wang X., Sun Q. Oncogenic MicroRNA-27a is a target for genistein in ovarian cancer cells. Anticancer Agents Med. Chem. 2013; 13 (7): 1126–32.
  111. Li H., Xu H., Shen H. microRNA-106a modulates cisplatin sensitivity by target-ing PDCD4 in human ovarian cancer cells. Oncol. Lett. 2013; 7 (1): 183–8.
  112. Cappellesso R., Tinazzi A., Giurici T., Simonato F., Guzzardo V., Ventura L., Crescenzi M., Chiarelli S., Fassina A. Pro-grammed cell death 4 and microRNA 21 inverse expression is maintained in cells and exosomes from ovarian serous car-cinoma effusions. Cancer Cytopathol. 2014; 122 (9): 685–93.
  113. Li J., Jiang K., Zhao F. Icariin regulates the proliferation and apoptosis of human ovarian cancer cells through microR-NA-21 by targeting PTEN, RECK and Bcl-2. Oncol. Rep. 2015; 33 (6): 2829–36.
  114. Parikh A., Lee C., Joseph P., Marchini S., Baccarini A., Kolev V., Romualdi C., Frus-cio R., Shah H., Wang F. et al. microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial-mesenchymal transition. Nat Commun. 2014; 5: 2977.
  115. Xia Y., Gao Y. MicroRNA-181b promotes ovarian cancer cell growth and invasion by targeting LATS2. Biochem. Biophys Res Commun. 2014; 447 (3): 446–51.
  116. Fang Y., Xu C., Fu Y. MicroRNA-17-5p induces drug resistance and invasion of ovarian carcinoma cells by targeting PTEN signaling. J. Biol. Res (Thessalon). 2015; 22: 12.
  117. Liu T., Qin W., Hou L., Huang Y. Micro-RNA-17 promotes normal ovarian cancer cells to cancer stem cells development via suppression of the LKB1-p53-p21/WAF1 pathway. Tumour Biol. 2014; 36 (3): 1881–93.
  118. Shuang T., Shi C., Chang S., Wang M., Bai C.H. Downregulation of miR-17~92 Expression Increase Paclitaxel Sensitivity in Human Ovarian Carcinoma SKOV3-TR30 Cells via BIM Instead of PTEN. Int J. Mol. Sci. 2013; 14 (2): 3802–16.
  119. Ye G., Fu G., Cui S., Zhao S., Bernaudo S., Bai Y., Ding Y., Zhang Y., Yang B.B., Peng C. MicroRNA 376c enhances ovarian cancer cell survival by targeting activin receptor-like kinase 7: implications for chemoresistance. J. Cell Sci. 2011; 124 (3): 359–68.
  120. Xu X., Dong Z., Li Y., Yang Y., Yuan Z., Qu X., Kong B. The upregulation of signal transducer and activator of transcrip-tion 5-dependent microRNA-182 and microRNA-96 promotes ovarian cancer cell proliferation by targeting forkhead box O3 upon leptin stimulation. Int J. Biochem. Cell Biol. 2012; 45 (3): 536–45.
  121. Weiner-Gorzel K., Dempsey E., Milewska M., McGoldrick A., Toh V., Walsh A., Lindsay S., Gubbins L., Cannon A., Sharpe D. et al. Overexpression of the microRNA miR-433 promotes resistance to paclitaxel through the induction of cellular senes-cence in ovarian cancer cells. Cancer Med. 2015; 4 (5): 745–58.
  122. Hu X., Macdonald D.M., Huettner P.C., Feng Z., El Naqa I.M., Schwarz J.K., Mutch D.G., Grigsby P.W., Powell S.N., Wang X. A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer. Gynecol. Oncol. 2009; 114 (3): 457–64
  123. Resnick K.E., Alder H., Hagan J.P., Richardson D.L., Croce C.M., Cohn D.E. The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol. Oncol. 2009; 112 (1): 55–9.
  124. Gao Y.C., Wu J. MicroRNA-200c and microRNA-141 as potential diagnostic and prognostic biomarkers for ovar-ian cancer. Tumour Biol. 2015; 36 (6): 4843–50.
  125. Chung Y.W., Bae H.S., Song J.Y., Lee J.K., Lee N.W., Kim T., Lee K.W. Detection of mi-croRNA as novel biomarkers of epithelial ovarian cancer from the serum of ovarian cancer patients. Int J. Gynecol. Cancer. 2013; 23 (4): 673–9.
  126. Chao A., Lai C.H., Chen H.C., Lin C.Y., Tsai C.L., Tang Y.H., Huang H.J., Lin C.T., Chen M.Y., Huang K.G. et al. Serum microRNAs in clear cell carcinoma of the ovary. Taiwan J. Obstet Gynecol. 2014; 53 (4): 536–41.
  127. Guo F., Tian J., Lin Y., Jin Y., Wang L., Cui M. Serum microRNA-92 expression in patients with ovarian epithelial carcinoma. J. Int Med. Res. 2013; 41 (5): 1456–61
  128. Hong F., Li Y., Xu Y., Zhu L. Prognostic signifi-cance of serum microRNA-221 expression in human epithelial ovarian cancer. J. Int Med. Res. 2013; 41 (1): 64–71.
  129. Ji T., Zheng Z.G., Wang F.M., Xu L.J., Li L.F., Cheng Q.H., Guo J.F., Ding X.F. Differential microRNA expression by Solexa sequenc-ing in the sera of ovarian cancer patients. Asian Pac J. Cancer Prev. 2014; 15 (4): 1739–43.
  130. Kan C.W., Hahn M.A., Gard G.B., Maidens J., Huh J.Y., Marsh D.J., Howell V.M. Ele-vated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer. BMC Cancer. 2013; 12: 627.
  131. Langhe R., Norris L., Saadeh F.A., Black-shields G., Varley R., Harrison A., Gleeson N., Spillane C., Martin C., O’Donnell D.M. et al. A novel serum microRNA panel to discriminate benign from malignant ovar-ian disease. Cancer Lett. 2015; 356 (2): 628–36
  132. Liang H., Jiang Z., Xie G., Lu Y. Serum microRNA-145 as a novel biomarker in human ovarian cancer. Tumour Biol. 2015; 36 (7): 5305–13.
  133. Xu Y.Z., Xi Q.H., Ge W.L., Zhang X.Q. Identification of serum microRNA-21 as a biomarker for early detection and prog-nosis in human epithelial ovarian cancer. Asian Pac J. Cancer Prev. 2013; 14 (2): 1057–60.
  134. Ayaz L., Cayan F., Balci S., Gorur A., Akbayir S., Yildirim Yaroglu H., Dogruer Unal N., Tamer L. Circulating microRNA expression profiles in ovarian cancer. J. Obstet Gynaecol. 2014; 34 (7): 620–4.
  135. Blondal T., Jensby Nielsen S., Baker A., Andreasen D., Mouritzen P., Wrang Teilum M., Dahlsveen I.K. Assessing sample and miRNA profile quality in serum and plasma or other biofluids. Methods. 2013; 59 (1): 1–6.
  136. Wang Z.H., Xu C.J. Research Progress of MicroRNA in Early Detection of Ovarian Cancer. Chin. Med. J. (Engl). 2015; 128 (24): 3363–70.
  137. Quitadamo A., Tian L., Hall B., Shi X. An integrated network of microRNA and gene expression in ovarian cancer. BMC Bioinformatics. 2015; 16 (5): 5.
  138. Wan Y.W., Mach C.M., Allen G.I., Ander-son M.L., Liu Z. On the reproducibility of TCGA ovarian cancer microRNA profiles. PLoS One. 2014; 9 (1): 87782.