Biochemistry (Moscow)

, Volume 82, Issue 5, pp 529–541 | Cite as

Molecular mechanisms of ovarian carcinoma metastasis: Key genes and regulatory microRNAs

  • E. A. BragaEmail author
  • M. V. Fridman
  • N. E. Kushlinskii


Metastasis of primary tumors progresses stepwise — from change in biochemistry, morphology, and migratory patterns of tumor cells to the emergence of receptors on their surface that facilitate directional migration to target organs followed by the formation of a specific microenvironment in a target organ that helps attachment and survival of metastatic cells. A set of specific genes and signaling pathways mediate this process under control of microRNA. The molecular mechanisms underlying biological processes associated with tumor metastasis are reviewed in this publication using ovarian cancer, which exhibits high metastatic potential, as an example. Information and data on the genes and regulatory microRNAs involved in the formation of cancer stem cells, epithelial–mesenchymal transition, reducing focal adhesion, degradation of extracellular matrix, increasing migration activity of cancer cells, formation of spheroids, apoptosis, autophagy, angiogenesis, formation of metastases, and development of ascites are presented. Clusters of microRNAs (miR-145, miR-31, miR-506, miR-101) most essential for metastasis of ovarian cancer including the families of microRNAs (miR-200, miR-214, miR-25) with dual role, which is different in different histological types of ovarian cancer, are discussed in detail in a section of the review.


regulatory miRNAs key genes ovarian cancer metastasis 



AKT serine/threonine kinase


AXL receptor tyrosine kinase


brain-derived neurotrophic factor


Bcl-2 interacting mediator of cell death


cancer stem cells


C-X-C motif chemokine ligand 12


extracellular matrix


E2F transcription factor 2


epidermal growth factor receptor


epithelial–mesenchymal transition


mitogen-activated protein kinase


fibroblast growth factor receptor


hypoxia-inducible factor 1 alpha subunit


high-mobility group (non-histone chromosomal) protein isoform I-C


mesenchymal–epithelial transition


matrix metalloproteinase 2 (gelatinase A, type IV collagenase)


matrix metalloproteinase 9 (gelatinase B)


mammalian target of rapamycin


nuclear factor kappa B


Notch (Drosophila) homolog 1 (translocation-associated)


platelet-derived growth factor


phosphatidylinositol-4,5-bisphosphate 3-kinase


phosphatase and tensin homolog (phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase)


ribosomal protein S6 kinase


Ras-related C3 botulinum toxin substrate 1


Slug (chicken homolog), zinc finger protein


SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4


Snail family transcriptional repressor


SRY (sex determining region Y)-box 4/9 protein




sphingosine kinase 1


sphingosine-1-phosphate receptor 1/2


transforming growth factor beta


tumor protein P53


Twist family BHLH transcription factor


Unc-51 like autophagy-activating kinase 1


urokinase type plasminogen activator


vascular endothelial growth factor


vascular endothelial growth factor receptor


wingless-type MMTV integration site family


zinc finger and BTB domain-containing protein 10


zinc finger E-box binding homeobox 1/2


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  1. 1.
    Chikina, A. S., and Aleksandrova, A. Yu. (2014) The cellular mechanisms and regulation of metastasis formation, Mol. Biol., 48, 165–180.CrossRefGoogle Scholar
  2. 2.
    Chan, S. H., and Wang, L. H. (2015) Regulation of cancer metastasis by microRNAs, J. Biomed. Sci., 22, 9.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Gerstein, M. B., Kundaje, A., Hariharan, M., Landt, S. G., Yan, K. K., Cheng, C., Mu, X. J., Khurana, E., Rozowsky, J., Alexander, R., Min, R., Alves, P., Abyzov, A., Addleman, N., Bhardwaj, N., Boyle, A. P., Cayting, P., Charos, A., Chen, D. Z., Cheng, Y., Clarke, D., Eastman, C., Euskirche, G., Frietze, S., Fu, Y., Gertz, J., Grubert, F., Harmanci, A., Jain, P., Kasowski, M., Lacroute, P., Leng, J., Lian, J., Monahan, H., O’Geen, H., Ouyang, Z., Partridge, E. C., Patacsil, D., Pauli, F., Raha, D., Ramirez, L., Reddy, T. E., Reed, B., Shi, M., Slifer, T., Wang, J., Wu, L., Yang, X., Yip, K. Y., Zilberman-Schapira, G., Batzoglou, S., Sidow, A., Farnham, P. J., Myers, R. M., Weissman, S. M., and Snyder, M. (2012) Architecture of the human regulatory network derived from ENCODE data, Nature, 489, 91–100.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Loginov, V. I., Rykov, S. V., Fridman, M. V., and Braga, E. A. (2015) Methylation of miRNA genes and oncogenesis, Biochemistry (Moscow), 80, 145–162.CrossRefGoogle Scholar
  5. 5.
    Lopez-Serra, P., and Esteller, M. (2012) DNA methylationassociated silencing of tumor suppressor microRNAs in cancer, Oncogene, 31, 1609–1622.CrossRefPubMedGoogle Scholar
  6. 6.
    Wang, Y., Kim, S., and Kim, I. M. (2014) Regulation of metastasis by microRNAs in ovarian cancer, Front. Oncol., 4, 143.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Chen, X., Zhang, J., Zhang, Z., Li, H., Cheng, W., and Liu, J. (2013) Cancer stem cells, epithelialmesenchymal transition, and drug resistance in highgrade ovarian serous carcinoma, Hum. Pathol., 44, 2373–2384.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Mittempergher, L. (2016) Genomic characterization of highgrade serous ovarian cancer: dissecting its molecular heterogeneity as a road towards effective therapeutic strategies, Curr. Oncol. Rep., 18, 44.CrossRefPubMedGoogle Scholar
  9. 9.
    Chakraborty, C., Chin, K. Y., and Das, S. (2016) miRNA-regulated cancer stem cells: understanding the property and the role of miRNA in carcinogenesis, Tumor Biol., 37, 13039–13048.CrossRefGoogle Scholar
  10. 10.
    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., and Cheng, J. Q. (2012) MicroRNA miR-214 regulates ovarian cancer cell stemness by targeting p53/Nanog, J. Biol. Chem., 287, 34970–34978.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Zaravinos, A. (2015) The regulatory role of microRNAs in EMT and cancer, J. Oncol., 865816.Google Scholar
  12. 12.
    Wellner, U., Schubert, J., Burk, U. C., Schmalhofer, O., Zhu, F., Sonntag, A., Waldvogel, B., Vannier, C., Darling, D., zur Hausen, A., Brunton, V. G., Morton, J., Sansom, O., Schuler, J., Stemmler, M. P., Herzberger, C., Hopt, U., Keck, T., Brabletz, S., and Brabletz, T. (2009) The EMT-activator ZEB1 promotes tumorigenicity by repressing stemnessinhibiting microRNAs, Nat. Cell. Biol., 11, 1487–1495.CrossRefPubMedGoogle Scholar
  13. 13.
    Yeh, Y. M., Chuang, C. M., Chao, K. C., and Wang, L. H. (2013) MicroRNA-138 suppresses ovarian cancer cell invasion and metastasis by targeting SOX4 and HIF-1α, Int. J. Cancer, 133, 867–878.CrossRefPubMedGoogle Scholar
  14. 14.
    Sun, Y., Guo, F., Bagnoli, M., Xue, F. X., Sun, B. C., Shmulevich, I., Mezzanzanica, D., Chen, K. X., Sood, A. K., Yang, D., and Zhang, W. (2015) Key nodes of a microRNA network associated with the integrated mesenchymal subtype of highgrade serous ovarian cancer, Chin. J. Cancer, 34, 28–40.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Dong, R., Liu, X., Zhang, Q., Jiang, Z., Li, Y., Wei, Y., Li, Y., Yang, Q., Liu, J., Wei, J. J., Shao, C., Liu, Z., and Kong, B. (2014) miR-145 inhibits tumor growth and metastasis by targeting metadherin in highgrade serous ovarian carcinoma, Oncotarget, 5, 10816–10829.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Mitra, A. K., Chiang, C. Y., Tiwari, P., Tomar, S., Watters, K. M., Peter, M. E., and Lengyel, E. (2015) Microenvironmentinduced downregulation of miR-193b drives ovarian cancer metastasis, Oncogene, 34, 5923–5932.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Li, H., Xu, Y., Qiu, W., Zhao, D., and Zhang, Y. (2015) Tissue miR-193b as a novel biomarker for patients with ovarian cancer, Med. Sci. Monit., 21, 3929–3934.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Cancer Genome Atlas Research Network (2011) Integrated genomic analyses of ovarian carcinoma, Nature, 474, 609–615.CrossRefGoogle Scholar
  19. 19.
    Yang, D., Sun, Y., Hu, L., Zheng, H., Ji, P., Pecot, C. V., Zhao, Y., Reynolds, S., Cheng, H., Rupaimoole, R., Cogdell, D., Nykter, M., Broaddus, R., Rodriguez-Aguayo, C., Lopez-Berestein, G., Liu, J., Shmulevich, I., Sood, A. K., Chen, K., and Zhang, W. (2013) Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer, Cancer Cell, 23, 186–199.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Imam, J. S., Plyler, J. R., Bansal, H., Prajapati, S., Bansal, S., Rebeles, J., Chen, H. I., Chang, Y. F., Panneerdoss, S., Zoghi, B., Buddavarapu, K. C., Broaddus, R., Hornsby, P., Tomlinson, G., Dome, J., Vadlamudi, R. K., Pertsemlidis, A., Chen, Y., and Rao, M. K. (2012) Genomic loss of tumor suppressor miRNA-204 promotes cancer cell migration and invasion by activating AKT/mTOR/Rac1 signaling and actin reorganization, PLoS One, 7, e52397.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Wei, L. Q., Liang, H. T., Qin, D. C., Jin, H. F., Zhao, Y., and She, M. C. (2014) MiR-212 exerts suppressive effect on SKOV3 ovarian cancer cells through targeting HBEGF, Tumor Biol., 35, 12427–12434.CrossRefGoogle Scholar
  22. 22.
    Li, J., Li, D., and Zhang, W. (2016) Tumor suppressor role of miR-217 in human epithelial ovarian cancer by targeting IGF1R, Oncol. Rep., 35, 1671–1679.PubMedGoogle Scholar
  23. 23.
    Zhang, H., Wang, Q., Zhao, Q., and Di, W. (2013) MiR-124 inhibits the migration and invasion of ovarian cancer cells by targeting SphK1, J. Ovarian Res., 6, 84.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Wen, Z., Zhao, S., Liu, S., Liu, Y., Li, X., and Li, S. (2015) MicroRNA-148a inhibits migration and invasion of ovarian cancer cells via targeting sphingosine-1-phosphate receptor 1, Mol. Med. Rep., 12, 3775–3780.PubMedGoogle Scholar
  25. 25.
    Li, P., Sun, Y., and Liu, Q. (2016) MicroRNA-340 induces apoptosis and inhibits metastasis of ovarian cancer cells by inactivation of NF-x03BA;B1, Cell. Physiol. Biochem., 38, 1915–1927.CrossRefPubMedGoogle Scholar
  26. 26.
    Chen, S., Chen, X., Xiu, Y. L., Sun, K. X., and Zhao, Y. (2015) Inhibition of ovarian epithelial carcinoma tumorigenesis and progression by microRNA 106b mediated through the RhoC pathway, PLoS One, 10, e0125714.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Lin, K. T., Yeh, Y. M., Chuang, C. M., Yang, S. Y., Chang, J. W., Sun, S. P., Wang, Y. S., Chao, K. C., and Wang, L. H. (2015) Glucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer metastasis through targeting Rap1B, Nat. Commun., 6, 5917.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Cowden Dahl, K. D., Dahl, R., Kruichak, J. N., and Hudson, L. G. (2009) The epidermal growth factor receptor responsive miR-125a represses mesenchymal morphology in ovarian cancer cells, Neoplasia, 11, 1208–1215.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Yang, Y., Jiang, Y., Wan, Y., Zhang, L., Qiu, J., Zhou, S., and Cheng, W. (2016) UCA1 functions as a competing endogenous RNA to suppress epithelial ovarian cancer metastasis, Tumor Biol., 37, 10633–10641.CrossRefGoogle Scholar
  30. 30.
    Vang, S., Wu, H. T., Fischer, A., Miller, D. H., MacLaughlan, S., Douglass, E., Comisar, L., Steinhoff, M., Collins, C., Smith, P. J., Brard, L., and Brodsky, A. S. (2013) Identification of ovarian cancer metastatic miRNAs, PLoS One, 8, e58226.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Pan, Y., Robertson, G., Pedersen, L., Lim, E., Hernandez-Herrera, A., Rowat, A. C., Patil, S. L., Chan, C. K., Wen, Y., Zhang, X., Basu-Roy, U., Mansukhani, A., Chu, A., Sipahimalani, P., Bowlby, R., Brooks, D., Thiessen, N., Coarfa, C., Ma, Y., Moore, R. A., Schein, J. E., Mungall, A. J., Liu, J., Pecot, C. V., Sood, A. K., Jones, S. J., Marra, M. A., and Gunaratne, P. H. (2016) miR-509-3p is clinically significant and strongly attenuates cellular migration and multicellular spheroids in ovarian cancer, Oncotarget, 7, 25930–25948.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Lin, J., Zhang, L., Huang, H., Huang, Y., Huang, L., Wang, J., Huang, S., He, L., Zhou, Y., Jia, W., Yun, J., Luo, R., and Zheng, M. (2015) MiR-26b/KPNA2 axis inhibits epithelial ovarian carcinoma proliferation and metastasis through downregulating OCT4, Oncotarget, 6, 23793–23806.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Lam, S. S., Ip, C. K., Mak, A. S., and Wong, A. S. (2016) A novel p70 S6 kinase–microRNA biogenesis axis mediates multicellular spheroid formation in ovarian cancer progression, Oncotarget, 7, 38064–38077.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Titone, R., Morani, F., Follo, C., Vidoni, C., Mezzanzanica, D., and Isidoro, C. (2014) Epigenetic control of autophagy by microRNAs in ovarian cancer, Biomed. Res. Int., 2014, 343542.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Fang, Y., Xu, C., and Fu, Y. (2015) MicroRNA-17-5p induces drug resistance and invasion of ovarian carcinoma cells by targeting PTEN signaling, J. Biol. Res. (Thessalon), 22, 12.CrossRefGoogle Scholar
  36. 36.
    Lou, Y., Yang, X., Wang, F., Cui, Z., and Huang, Y. (2010) 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., 26, 819–827.CrossRefPubMedGoogle Scholar
  37. 37.
    Penna, E., Orso, F., and Taverna, D. (2015) miR-214 as a key hub that controls cancer networks: small player, multiple functions, J. Invest. Dermatol., 135, 960–969.CrossRefPubMedGoogle Scholar
  38. 38.
    Shen, Y., Li, D. D., Wang, L. L., Deng, R., and Zhu, X. F. (2008) Decreased expression of autophagyrelated proteins in malignant epithelial ovarian cancer, Autophagy, 4, 1067–1068.CrossRefPubMedGoogle Scholar
  39. 39.
    Bunkholt, E. M., Dong, H. P., Odegaard, E., Holth, A., Elloul, S., Reich, R., Trope, C. G., and Davidson, B. (2010) Mammalian target of rapamycin is a biomarker of poor survival in metastatic serous ovarian carcinoma, Hum. Pathol., 41, 794–804.CrossRefGoogle Scholar
  40. 40.
    Vecchione, A., Belletti, B., Lovat, F., Volinia, S., Chiappetta, G., Giglio, S., Sonego, M., Cirombella, R., Onesti, E. C., Pellegrini, P., Califano, D., Pignata, S., Losito, S., Canzonieri, V., Sorio, R., Alder, H., Wernicke, D., Stoppacciaro, A., Baldassarre, G., and Croce, C. M. (2013) A microRNA signature defines chemoresistance in ovarian cancer through modulation of angiogenesis, Proc. Natl. Acad. Sci. USA, 110, 9845–9850.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Luo, Z., Wang, Q., Lau, W. B., Lau, B., Xu, L., Zhao, L., Yang, H., Feng, M., Xuan, Y., Yang, Y., Lei, L., Wang, C., Yi, T., Zhao, X., Wei, Y., and Zhou, S. (2016) Tumor microenvironment: the culprit for ovarian cancer metastasis? Cancer Lett., 377, 174–182.CrossRefPubMedGoogle Scholar
  42. 42.
    Joshi, H. P., Subramanian, I. V., Schnettler, E. K., Ghosh, G., Rupaimoole, R., Evans, C., Saluja, M., Jing, Y., Cristina, I., Roy, S., Zeng, Y., Shah, V. H., Sood, A. K., and Ramakrishnan, S. (2014) Dynamin 2 along with microRNA-199a reciprocally regulate hypoxiainducible factors and ovarian cancer metastasis, Proc. Natl. Acad. Sci. USA, 111, 5331–5336.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Lv, Y., Lei, Y., Hu, Y., Ding, W., Zhang, C., and Fang, C. (2015) miR-448 negatively regulates ovarian cancer cell growth and metastasis by targeting CXCL12, Clin. Transl. Oncol., 17, 903–909.CrossRefPubMedGoogle Scholar
  44. 44.
    Schmid, G., Notaro, S., Reimer, D., Abdel-Azim, S., Duggan-Peer, M., Holly, J., Fiegl, H., Rössler, J., Wiedemair, A., Concin, N., Altevogt, P., Marth, C., and Zeimet, A. G. (2016) Expression and promotor hypermethylation of miR-34a in the various histological subtypes of ovarian cancer, BMC Cancer, 16, 102.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Li, R., Shi, X., Ling, F., Wang, C., Liu, J., Wang, W., and Li, M. (2015) MiR-34a suppresses ovarian cancer proliferation and motility by targeting AXL, Tumor Biol., 36, 7277–7283.CrossRefGoogle Scholar
  46. 46.
    Dong, P., Xiong, Y., Watari, H., Hanley, S. J., Konno, Y., Ihira, K., Yamada, T., Kudo, M., Yue, J., and Sakuragi, N. (2016) MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphereforming ability of ovarian cancer cells, J. Exp. Clin. Cancer Res., 35, 132.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Kim, T. H., Song, J. Y., Park, H., Jeong, J. Y., Kwon, A. Y., Heo, J. H., Kang, H., Kim, G., and An, H. J. (2015) miR-145, targeting highmobility group A2, is a powerful predictor of patient outcome in ovarian carcinoma, Cancer Lett., 28, 937–945.CrossRefGoogle Scholar
  48. 48.
    Chen, X., Dong, C., Law, P., Chan, M. T., Su, Z., Wang, S., Wu, W. K., and Xu, H. (2015) MicroRNA-145 targets TRIM2 and exerts tumorsuppressing functions in epithelial ovarian cancer, Gynecol. Oncol., 139, 513–519.CrossRefPubMedGoogle Scholar
  49. 49.
    Zhang, W., Wang, Q., Yu, M., Wu, N., and Wang, H. (2014) MicroRNA-145 function as a cell growth repressor by directly targeting c-Myc in human ovarian cancer, Technol. Cancer Res. Threat., 13, 161–168.Google Scholar
  50. 50.
    Xu, Q., Liu, L. Z., Qian, X., Chen, Q., Jiang, Y., Li, D., Lai, L., and Jiang, B. H. (2012) MiR-145 directly targets p70S6K1 in cancer cells to inhibit tumor growth and angiogenesis, Nucleic Acids Res., 40, 761–774.CrossRefPubMedGoogle Scholar
  51. 51.
    Creighton, C. J., Fountain, M. D., Yu, Z., Nagaraja, A. K., Zhu, H., Khan, M., Olokpa, E., Zariff, A., Gunaratne, P. H., Matzuk, M. M., and Anderson, M. L. (2010) Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers, Cancer Res., 70, 1906–1915.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Mitamura, T., Watari, H., Wang, L., Kanno, H., Hassan, M. K., Miyazaki, M., Katoh, Y., Kimura, T., Tanino, M., Nishihara, H., Tanaka, S., and Sakuragi, N. (2013) Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET, Oncogenesis, 25, e40.CrossRefGoogle Scholar
  53. 53.
    Guo, F., Cogdell, D., Hu, L., Yang, D., Sood, A. K., Xue, F., and Zhang, W. (2014) MiR-101 suppresses the epithelialtomesenchymal transition by targeting ZEB1 and ZEB2 in ovarian carcinoma, Oncol. Rep., 31, 2021–2028.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Kinose, Y., Sawada, K., Nakamura, K., and Kimura, T. (2014) The role of microRNAs in ovarian cancer, Biomed. Res. Int., 249393.Google Scholar
  55. 55.
    Sulaiman, S. A., Ab Mutalib, N. S., and Jamal, R. (2016) miR-200c regulation of metastases in ovarian cancer: potential role in epithelial and mesenchymal transition, Front. Pharmacol., 7, 271.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Tang, M. K., and Wong, A. S. (2015) Exosomes: emerging biomarkers and targets for ovarian cancer, Cancer Lett., 367, 26–33.CrossRefPubMedGoogle Scholar
  57. 57.
    Gong, C., Yang, Z., Wu, F., Han, L., Liu, Y., and Gong, W. (2016) miR-17 inhibits ovarian cancer cell peritoneal metastasis by targeting ITGA5 and ITGB1, Oncol. Rep., 36, 2177–2183.PubMedGoogle Scholar
  58. 58.
    Xie, J., Liu, M., Li, Y., Nie, Y., Mi, Q., and Zhao, S. (2014) Ovarian tumorassociated microRNA-20a decreases natural killer cell cytotoxicity by downregulating MICA/B expression, Cell Mol. Immunol., 11, 495–502.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Yan, J., Jiang, J. Y., Meng, X. N., Xiu, Y. L., and Zong, Z. H. (2016) MiR-23b targets cyclin G1 and suppresses ovarian cancer tumorigenesis and progression, J. Clin. Cancer Res., 35, 31.CrossRefGoogle Scholar
  60. 60.
    Ibrahim, F. F., Jamal, R., Syafruddin, S. E., Ab Mutalib, N. S., Saidin, S., MdZin, R. R., Hossain Mollah, M. M., and Mokhtar, N. M. (2015) MicroRNA-200c and microRNA-31 regulate proliferation, colony formation, migration and invasion in serous ovarian cancer, J. Ovarian Res., 8, 56.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Chen, L., Zhang, F., Sheng, X. G., Zhang, S. Q., Chen, Y. T., and Liu, B. W. (2016) MicroRNA-106a regulates phosphatase and tensin homologue expression and promotes the proliferation and invasion of ovarian cancer cells, Oncol. Rep., 36, 2135–2141.PubMedGoogle Scholar
  62. 62.
    Chen, S., Chen, X., Xiu, Y. L., Sun, K. X., and Zhao, Y. (2015) Inhibition of ovarian epithelial carcinoma tumorigenesis and progression by microRNA 106b mediated through the RhoC pathway, PLoS One, 10, e0125714.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Chai, Y., Liu, J., Zhang, Z., and Liu, L. (2016) HuR-regulated lncRNA NEAT1 stability in tumorigenesis and progression of ovarian cancer, Cancer Med., 5, 1588–1598.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Wang, L., He, J., Xu, H., Xu, L., and Li, N. (2016) MiR-143 targets CTGF and exerts tumorsuppressing functions in epithelial ovarian cancer, Am. J. Transl. Res., 8, 2716–2726.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Jin, M., Yang, Z., Ye, W., Xu, H., and Hua, X. (2014) MicroRNA-150 predicts a favorable prognosis in patients with epithelial ovarian cancer, and inhibits cell invasion and metastasis by suppressing transcriptional repressor ZEB1, PLoS One, 9, e103965.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Liang, T., Li, L., Cheng, Y., Ren, C., and Zhang, G. (2016) MicroRNA-194 promotes the growth, migration, and invasion of ovarian carcinoma cells by targeting protein tyrosine phosphatase nonreceptor type 12, Onco Targets Ther., 9, 4307–4315.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Niu, K., Shen, W., Zhang, Y., Zhao, Y., and Lu, Y. (2015) MiR-205 promotes motility of ovarian cancer cells via targeting ZEB1, Gene, 574, 330–336.CrossRefPubMedGoogle Scholar
  68. 68.
    Zhang, Y., Shi, B., Chen, J., Hu, L., and Zhao, C. (2016) MiR-338-3p targets pyruvate kinase M2 and affects cell proliferation and metabolism of ovarian cancer, Am. J. Transl. Res., 8, 3266–3273.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Zhang, Z., Cheng, J., Wu, Y., Qiu, J., Sun, Y., and Tong, X. (2016) LncRNA HOTAIR controls the expression of Rab22a by sponging miR-373 in ovarian cancer, Mol. Med. Rep., 14, 2465–2472.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Sun, Y., Hu, L., Zheng, H., Bagnoli, M., Guo, Y., Rupaimoole, R., Rodriguez-Aguayo, C., Lopez-Berestein, G., Ji, P., Chen, K., Sood, A. K., Mezzanzanica, D., Liu, J., Sun, B., and Zhang, W. (2015) MiR-506 inhibits multiple targets in the epithelialtomesenchymal transition network and is associated with good prognosis in epithelial ovarian cancer, J. Pathol., 235, 25–36.CrossRefPubMedGoogle Scholar
  71. 71.
    Rupaimoole, R., Ivan, C., Yang, D., Gharpure, K. M., Wu, S. Y., Pecot, C. V., Previs, R. A., Nagaraja, A. S., Armaiz-Pena, G. N., McGuire, M., Pradeep, S., Mangala, L. S., Rodriguez-Aguayo, C., Huang, L., Bar-Eli, M., Zhang, W., Lopez-Berestein, G., Calin, G. A., and Sood, A. K. (2016) Hypoxiaupregulated microRNA-630 targets Dicer, leading to increased tumor progression, Oncogene, 35, 4312–4320.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Wang, Y., Yan, S., Liu, X., Zhang, W., Li, Y., Dong, R., Zhang, Q., Yang, Q., Yuan, C., Shen, K., and Kong, B. (2014) miR-1236-3p represses the cell migration and invasion abilities by targeting ZEB1 in highgrade serous ovarian carcinoma, Oncol. Rep., 31, 1905–1910.PubMedGoogle Scholar
  73. 73.
    Piletic, K., and Kunej, T. (2016) MicroRNA epigenetic signatures in human disease, Arch. Toxicol., 90, 2405–2419.CrossRefPubMedGoogle Scholar
  74. 74.
    Baylin, S. B., and Jones, P. A. (2016) Epigenetic determinants of cancer, Cold Spring Harb. Perspect. Biol., 8, a019505.CrossRefGoogle Scholar
  75. 75.
    Malladi, S., Macalinao, D. G., Jin, X., He, L., Basnet, H., Zou, Y., De Stanchina, E., and Massague, J. (2016) Metastatic latency and immune evasion through autocrine inhibition of WNT, Cell, 165, 45–60.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  • E. A. Braga
    • 1
    Email author
  • M. V. Fridman
    • 1
    • 2
  • N. E. Kushlinskii
    • 3
  1. 1.Institute of General Pathology and PathophysiologyMoscowRussia
  2. 2.Vavilov Institute of General GeneticsRussian Academy of SciencesMoscowRussia
  3. 3.Blokhin Cancer Research CenterMoscowRussia

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