Skip to main content
SpringerLink
Log in

Molecular mechanisms and microRNAs in osteosarcoma pathogenesis

  • Review
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

This review summarizes data on microRNA (miRNA) genomic organization, biogenesis, and functions in carcinogenesis. The roles of key genes and regulatory miRNAs in molecular mechanisms and signaling pathways involved in the development of osteosarcoma, the most aggressive type of bone tumor striking mainly in adolescence and early adulthood, are discussed in detail. The most critical pathways in osteosarcoma pathogenesis are the Notch, Wnt, NF-κB, p53, PI3K/Akt, and MAPK pathways. The balance between cell survival and apoptosis is determined by the Wnt and NF-κB pathways, as well as by the ratio between the activities of the MAPK and PI3K/Akt pathways. Several miRNAs (miR-21, -34a, -143, -148a, -195a, -199a-3p, -382) regulate multiple target genes, pathways, and processes essential for osteosarcoma pathogenesis. Data on the key genes and regulatory miRNAs involved in metastasis and tumor cell response to drug treatment are presented. Possible applications of miRNA in osteosarcoma diagnostics and treatment are discussed.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kushlinskii, N. E., Timofeev, Yu. S., Shirshova, A. N., Gordukova, M. A., Philipenko, M. L., Gershtein, E. S., and Senjapova, E. R. (2014) Osteosarcoma-Specific MicroRNA (miRNA) Levels in Blood Plasma of Patients and Healthy Persons. Book of Abstracts of 27th Annual Meeting of the European Musculo-Skeletal Oncology Society, May 21-23, 2014, Vienna, Austria, pp. 56–57.

    Google Scholar 

  2. Kobayashi, E., Hornicek, F. J., and Duan, Z. (2012) MicroRNA involvement in osteosarcoma, Sarcoma, 359739.

  3. Kafchinski, L. A., and Jones, K. B. (2014) MicroRNAs in osteosarcomagenesis, Adv. Exp. Med. Biol., 804, 119–127.

    Article  CAS  PubMed  Google Scholar 

  4. Dweep, H., Sticht, C., Pandey, P., and Gretz, N. (2011) miRWalk database: prediction of possible miRNA binding sites by “walking” the genes of three genomes, J. Biomed. Inform., 44, 839–847.

    Article  CAS  PubMed  Google Scholar 

  5. Wightman, B., Ha, I., and Ruvkun, G. (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans, Cell, 75, 855–862.

    Article  CAS  PubMed  Google Scholar 

  6. Reinhart, B. J., Slack, F. J., Basson, M., Pasquinelli, A. E., Bettinger, J. C., Rougvie, A. E., Horvitz, H. R., and Ruvkun, G. (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans, Nature, 403, 901–906.

    Article  CAS  PubMed  Google Scholar 

  7. Pasquinelli, A. E., Reinhart, B. J., Slack, F., Martindale, M. Q., Kuroda, M. I., Maller, B., Hayward, D. C., Ball, E. E., Degnan, B., Muller, P., Spring, J., Srinivasan, A., Fishman, M., Finnerty, J., Corbo, J., Levine, M., Leahy, P., Davidson, E., and Ruvkun, G. (2000) Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA, Nature, 408, 86–89.

    Article  CAS  PubMed  Google Scholar 

  8. Kozomara, A., and Griffiths-Jones, S. (2014) miRBase: annotating high confidence microRNAs using deep sequencing data, Nucleic Acids Res., 42, 68–73.

    Article  Google Scholar 

  9. Lopez Serra, P., and Esteller, M. (2012) DNA methylation associated silencing of tumor-suppressor microRNAs in cancer, Oncogene, 31, 1609–1622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Friedman, R. C., Farh, K. K., Burge, C. B., and Bartel, D. P. (2009) Most mammalian mRNAs are conserved targets of microRNAs, Genome Res., 19, 92–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Griffiths-Jones, S., Saini, H. K., Van Dongen, S., and Enright, A. J. (2008) miRBase: tools for microRNA genomics, Nucleic Acids Res., 36, 154–158.

    Article  Google Scholar 

  12. Olive, V., Jiang, I., and He, L. (2010) miR-17-92, a cluster of miRNAs in the midst of the cancer network, Int. J. Biochem. Cell Biol., 42, 1348–1354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Saini, H. K., Griffiths-Jones, S., and Enright, A. J. (2007) Genomic analysis of human microRNA transcripts, Proc. Natl. Acad. Sci. USA, 104, 17719–17724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cullen, B. R. (2004) Transcription and processing of human microRNA precursors, Mol. Cell, 16, 861–865.

    Article  CAS  PubMed  Google Scholar 

  15. Wang, D., Lu, M., Miao, J., Li, T., Wang, E., and Cui, Q. (2009) Cepred: predicting the co-expression patterns of the human intronic microRNAs with their host genes, PLoS One, 4, e4421.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lee, Y., Kim, M., Han, J., Yeom, K. H., Lee, S., Baek, S. H., and Kim, V. N. (2004) MicroRNA genes are transcribed by RNA polymerase II, EMBO J., 23, 4051–4060.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Borchert, G. M., Lanier, W., and Davidson, B. L. (2006) RNA polymerase III transcribes human microRNAs, Nat. Struct. Mol. Biol., 13, 1097–1101.

    Article  CAS  PubMed  Google Scholar 

  18. Macfarlane, L. A., and Murphy, P. R. (2010) MicroRNA: biogenesis, function and role in cancer, Curr. Genom., 11, 537–561.

    Article  CAS  Google Scholar 

  19. Graves, P., and Zeng, Y. (2012) Most mammalian mRNAs are conserved targets of microRNAs: a global view, Genom. Proteom. Bioinform., 10, 239–245.

    Article  CAS  Google Scholar 

  20. Calin, G. A., Cimmino, A., Fabbri, M., Ferracin, M., Wojcik, S. E., Shimizu, M., Taccioli, C., Zanesi, N., Garzon, R., Aqeilan, R. I., Alder, H., Volinia, S., Rassenti, L., Liu, X., Liu, C. G., Kipps, T. J., Negrini, M., and Croce, C. M. (2008) miR-15a and miR-16-1 cluster functions in human leukemia, Proc. Natl. Acad. Sci. USA, 105, 5166–5171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fabbri, M. (2010) miRNAs as molecular biomarkers of cancer, Expert. Rev. Mol. Diagn., 10, 435–444.

    Article  CAS  PubMed  Google Scholar 

  22. Lebanony, D., Benjamin, H., Gilad, S., Ezagouri, M., Dov, A., Ashkenazi, K., Gefen, N., Izraeli, S., Rechavi, G., Pass, H., Nonaka, D., Li, J., Spector, Y., Rosenfeld, N., Chajut, A., Cohen, D., Aharonov, R., and Mansukhani, M. (2009) Diagnostic assay based on hsa-miR-205 expression distinguishes squamous from nonsquamous non-small-cell lung carcinoma, J. Clin. Oncol., 27, 2030–2037.

    Article  CAS  PubMed  Google Scholar 

  23. Landi, M. T., Zhao, Y., Rotunno, M., Koshiol, J., Liu, H., Bergen, A. W., Rubagotti, M., Goldstein, A. M., Linnoila, I., Marincola, F. M., Tucker, M. A., Bertazzi, P. A., Pesatori, A. C., Caporaso, N. E., McShane, L. M., and Wang, E. (2010) MicroRNA expression differentiates histology and predicts survival of lung cancer, Clin. Cancer Res., 16, 430–441.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Papagiannakopoulos, T., Shapiro, A., and Kosik, K. S. (2008) MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells, Cancer Res., 68, 8164–8172.

    Article  CAS  PubMed  Google Scholar 

  25. Si, M. L., Zhu, S., Wu, H., Lu, Z., Wu, F., and Mo, Y. Y. (2007) miR-21-mediated tumor growth, Oncogene, 26, 2799–2803.

    Article  CAS  PubMed  Google Scholar 

  26. He, L., He, X., Lim, L. P., De Stanchina, E., Xuan, Z., Liang, Y., Xue, W., Zender, L., Magnus, J., Ridzon, D., Jackson, A. L., Linsley, P. S., Chen, C., Lowe, S. W., Cleary, M. A., and Hannon, G. J. (2007) A microRNA component of the p53 tumor suppressor network, Nature, 447, 1130–1134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hermeking, H. (2010) The miR-34 family in cancer and apoptosis, Cell Death Differ., 17, 193–199.

    Article  CAS  PubMed  Google Scholar 

  28. Wang, R., Ma, J., Wu, Q., Xia, J., Miele, L., Sarkar, F. H., and Wang, Z. (2013) Functional role of miR-34 family in human cancer, Curr. Drug Targets, 14, 1185–1191.

    Article  CAS  PubMed  Google Scholar 

  29. Choudhury, S. N., and Li, Y. (2012) miR-21 and let-7 in the Ras and NF-κB pathways, MicroRNA, 1, 65–69.

    Article  CAS  PubMed  Google Scholar 

  30. Lee, S. T., Chu, K., Oh, H. J., Im, W. S., Lim, J. Y., Kim, S. K., Park, C. K., Jung, K. H., Lee, S. K., Kim, M., and Roh, J. K. (2011) Let-7 microRNA inhibits the proliferation of human glioblastoma cells, J. Neurooncol., 102, 19–24.

    Article  CAS  PubMed  Google Scholar 

  31. Qian, P., Zuo, Z., Wu, Z., Meng, X., Li, G., Wu, Z., Zhang, W., Tan, S., Pandey, V., Yao, Y., Wang, P., Zhao, L., Wang, J., Wu, Q., Song, E., Lobie, P. E., Yin, Z., and Zhu, T. (2011) Pivotal role of reduced let-7g expression in breast cancer invasion and metastasis, Cancer Res., 71, 6463–6474.

    Article  CAS  PubMed  Google Scholar 

  32. Nadiminty, N., Tummala, R., Lou, W., Zhu, Y., Shi, X. B., Zou, J. X., Chen, H., Zhang, J., Chen, X., Luo, J., deVere White, R. W., Kung, H. J., Evans, C. P., and Gao, A. C. (2012) MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth, PLoS One, 7, e32832.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang, S., Tang, Y., Cui, H., Zhao, X., Luo, X., Pan, W., Huang, X., and Shen, N. (2011) Let-7/miR-98 regulate Fas and Fas-mediated apoptosis, Genes Immun., 12, 149–154.

    Article  PubMed  Google Scholar 

  34. Hanahan, D., and Weinberg, R. A. (2011) Hallmarks of cancer: the next generation, Cell, 144, 646–674.

    Article  CAS  PubMed  Google Scholar 

  35. Deng, S., Calin, G. A., Croce, C. M., Coukos, G., and Zhang, L. (2008) Mechanisms of microRNA deregulation in human cancer, Cell Cycle, 7, 2643–2646.

    Article  CAS  PubMed  Google Scholar 

  36. Calin, G. A., and Croce, C. M. (2006) MicroRNA signatures in human cancers, Nat. Rev. Cancer, 6, 857–866.

    Article  CAS  PubMed  Google Scholar 

  37. Arroyo, J. D., Chevillet, J. R., Kroh, E. M., Ruf, I. K., Pritchard, C. C., Gibson, D. F., Mitchell, P. S., Bennett, C. F., Pogosova-Agadjanyan, E. L., Stirewalt, D. L., Tait, J. F., and Tewari, M. (2011) Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma, Proc. Natl. Acad. Sci. USA, 108, 5003–5008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gajos-Michniewicz, A., Duechler, M., and Czyz, M. (2014) MiRNA in melanoma-derived exosomes, Cancer Lett., 347, 29–37.

    Article  CAS  PubMed  Google Scholar 

  39. Lim, P. K., Bliss, S. A., Patel, S. A., Taborga, M., Dave, M. A., Gregory, L. A., Greco, S. J., Bryan, M., Patel, P. S., and Rameshwar, P. (2011) Gap junction-mediated import of microRNA from bone marrow stromal cells can elicit cell cycle quiescence in breast cancer cells, Cancer Res., 71, 1550–1560.

    Article  CAS  PubMed  Google Scholar 

  40. He, J. P., Hao, Y., Wang, X. L., Yang, X. J., Shao, J. F., Guo, F. J., and Feng, J. X. (2014) Review of the molecular pathogenesis of osteosarcoma, Asian Pac. J. Cancer Prev., 15, 5967–5976.

    Article  PubMed  Google Scholar 

  41. Zhu, L., McManus, M. M., and Hughes, D. P. (2013) Understanding the biology of bone sarcoma from early initiating events through late events in metastasis and disease progression, Front. Oncol., 3, 230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhou, W., Hao, M., Du, X., Chen, K., Wang, G., and Yang, J. (2014) Advances in targeted therapy for osteosarcoma, Discov. Med., 17, 301–307.

    PubMed  Google Scholar 

  43. Ouellet, V., and Siegel, P. M. (2012) CCN3 modulates bone turnover and is a novel regulator of skeletal metastasis, J. Cell Commun. Signal., 6, 73–85.

    Article  PubMed  PubMed Central  Google Scholar 

  44. De Boer, J., Van Royen, B. J., and Helder, M. N. (2013) Mechanisms of therapy resistance in osteosarcoma: a review, Oncol. Discov., doi: org/10.7243/2052-6199-1-8.

    Google Scholar 

  45. Misso, G., Di Martino, M. T., De Rosa, G., Farooqi, A. A., Lombardi, A., Campani, V., Zarone, M. R., Gulla, A., Tagliaferri, P., Tassone, P., and Caraglia, M. (2014) Mir-34: a new weapon against cancer? Mol. Ther. Nucleic Acids, 3, e194.

    Article  CAS  PubMed  Google Scholar 

  46. Li, Y., Zhang, J., Zhang, L., Si, M., Yin, H., and Li, J. (2013) Diallyl trisulfide inhibits proliferation, invasion and angiogenesis of osteosarcoma cells by switching on suppressor microRNAs and inactivating of Notch-1 signaling, Carcinogenesis, 34, 1601–1610.

    Article  CAS  PubMed  Google Scholar 

  47. Lv, H., Pei, J., Liu, H., Wang, H., and Liu, J. (2014) A polymorphism site in the pre miR 34a coding region reduces miR 34a expression and promotes osteosarcoma cell proliferation and migration, Mol. Med. Rep., 10, 2912–2916.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Tian, Y., Zhang, Y. Z., and Chen, W. (2014) MicroRNA-199a-3p and microRNA-34a regulate apoptosis in human osteosarcoma cells, Biosci. Rep., 34, doi: 10.1042/BSR20140084.

  49. Shang, Y., Wang, L. Q., Guo, Q. Y., and Shi, T. L. (2015) MicroRNA-196a overexpression promotes cell proliferation and inhibits cell apoptosis through PTEN/Akt/FOXO1 pathway, Int. J. Clin. Exp. Pathol., 8, 2461–2472.

    PubMed  PubMed Central  Google Scholar 

  50. 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.

    Article  CAS  Google Scholar 

  51. Silva, G., and Aboussekhra, A. (2015) p16INK4A inhibits the pro-metastatic potentials of osteosarcoma cells through targeting the ERK pathway and TGF-ß1, Mol. Carcinog., doi: 10.1002/mc.22299.

    Google Scholar 

  52. Ziyan, W., Shuhua, Y., Xiufang, W., and Xiaoyun, L. (2011) MicroRNA-21 is involved in osteosarcoma cell invasion and migration, Med. Oncol., 28, 1469–1474.

    Article  PubMed  Google Scholar 

  53. Ziyan, W., and Yang, L. (2016) MicroRNA-21 regulates the sensitivity to cisplatin in a human osteosarcoma cell line, Ir. J. Med. Sci., 185, 85–91.

    Article  CAS  PubMed  Google Scholar 

  54. Duan, Z., Choy, E., Harmon, D., Liu, X., Susa, M., Mankin, H., and Hornicek, F. (2011) MicroRNA-199a-3p is downregulated in human osteosarcoma and regulates cell proliferation and migration, Mol. Cancer Ther., 10, 1337–1345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ouyang, L., Liu, P., Yang, S., Ye, S., Xu, W., and Liu, X. (2013) A three-plasma miRNA signature serves as novel biomarkers for osteosarcoma, Med. Oncol., 30, 340.

    Article  PubMed  Google Scholar 

  56. Zhang, H., Cai, X., Wang, Y., Tang, H., Tong, D., and Ji, F. (2010) microRNA-143, down-regulated in osteosarcoma, promotes apoptosis and suppresses tumorigenicity by targeting Bcl-2, Oncol. Rep., 24, 1363–1369.

    CAS  PubMed  Google Scholar 

  57. Osaki, M., Takeshita, F., Sugimoto, Y., Kosaka, N., Yamamoto, Y., Yoshioka, Y., Kobayashi, E., Yamada, T., Kawai, A., Inoue, T., Ito, H., Oshimura, M., and Ochiya, T. (2011) MicroRNA-143 regulates human osteosarcoma metastasis by regulating matrix metalloprotease-13 expression, Mol. Ther., 19, 1123–1130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ye, Z., Jingzhong, L., Yangbo, L., Lei, C., and Jiandong, Y. (2013) Propofol inhibits proliferation and invasion of osteosarcoma cells by regulation of microRNA-143 expression, Oncol. Res., 21, 201–207.

    Article  PubMed  Google Scholar 

  59. Li, F., Li, S., and Cheng, T. (2014) TGF-ß1 promotes osteosarcoma cell migration and invasion through the miR-143-versican pathway, Cell. Physiol. Biochem., 34, 2169–2179.

    Article  PubMed  Google Scholar 

  60. Ma, W., Zhang, X., Chai, J., Chen, P., Ren, P., and Gong, M. (2014) Circulating miR-148a is a significant diagnostic and prognostic biomarker for patients with osteosarcoma, Tumour Biol., 35, 12467–12472.

    Article  CAS  PubMed  Google Scholar 

  61. Chang, Y., Zhao, Y., Gu, W., Cao, Y., Wang, S., Pang, J., and Shi, Y. (2015) Bufalin inhibits the differentiation and proliferation of cancer stem cells derived from primary osteosarcoma cells through Mir-148a, Cell. Physiol. Biochem., 36, 1186–1196.

    Article  CAS  PubMed  Google Scholar 

  62. Han, K., Chen, X., Bian, N., Ma, B., Yang, T., Cai, C., Fan, Q., Zhou, Y., and Zhao, T. B. (2015) MicroRNA profiling identifies MiR-195 suppresses osteosarcoma cell metastasis by targeting CCND1, Oncotarget, 6, 8875–8889.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Lian, F., Cui, Y., Zhou, C., Gao, K., and Wu, L. (2015) Identification of a plasma four-microRNA panel as potential noninvasive biomarker for osteosarcoma, PLoS One, 10, e0121499.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Mao, J. H., Zhou, R. P., Peng, A. F., Liu, Z. L., Huang, S. H., Long, X. H., and Shu, Y. (2012) microRNA-195 suppresses osteosarcoma cell invasion and migration in vitro by targeting FASN, Oncol. Lett., 4, 1125–1129.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Cai, H., Zhao, H., Tang, J., and Wu, H. J. (2015) Serum miR-195 is a diagnostic and prognostic marker for osteosarcoma, Surg. Res., 194, 505–510.

    Article  CAS  Google Scholar 

  66. He, W., Feng, L., Xia, D., and Han, N. (2015) MiR-374a promotes the proliferation of human osteosarcoma by downregulating FOXO1 expression, Int. J. Clin. Exp. Med., 8, 3482–3489.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Zhu, J., Feng, Y., Ke, Z., Yang, Z., Zhou, J., Huang, X., and Wang, L. (2012) Down-regulation of miR-183 promotes migration and invasion of osteosarcoma by targeting Ezrin, Am. J. Pathol., 180, 2440–2451.

    Article  CAS  PubMed  Google Scholar 

  68. Mu, Y., Zhang, H., Che, L., and Li, K. (2014) Clinical significance of microRNA-183/Ezrin axis in judging the prognosis of patients with osteosarcoma, Med. Oncol., 31, 821.

    Article  PubMed  Google Scholar 

  69. Jones, K. B., Salah, Z., Del Mare, S., Galasso, M., Gaudio, E., Nuovo, G. J., Lovat, F., LeBlanc, K., Palatini, J., Randall, R. L., Volinia, S., Stein, G. S., Croce, C. M., Lian, J. B., and Aqeilan, R. I. (2012) MicroRNA signatures associate with pathogenesis and progression of osteosarcoma, Cancer Res., 72, 1865–1877.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Xu, M., Jin, H., Xu, C. X., Sun, B., Song, Z. G., Bi, W. Z., and Wang, Y. (2015) miR-382 inhibits osteosarcoma metastasis and relapse by targeting Y box-binding protein 1, Mol. Ther., 23, 89–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Thayanithy, V., Sarver, A. L., Kartha, R. V., Li, L., Angstadt, A. Y., Breen, M., Steer, C. J., Modiano, J. F., and Subramanian, S. (2012) Perturbation of 14q32 miRNAscMYC gene network in osteosarcoma, Bone, 50, 171–181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Sun, X. H., Geng, X. L., Zhang, J., and Zhang, C. (2015) miRNA-646 suppresses osteosarcoma cell metastasis by downregulating fibroblast growth factor 2 (FGF2), Tumour Biol., 36, 2127–2134.

    Article  CAS  PubMed  Google Scholar 

  73. Zhang, J., Li, S., Li, L., Li, M., Guo, C., Yao, J., and Mi, S. (2015) Exosome and exosomal microRNA: trafficking, sorting, and function, Genom. Proteom. Bioinform., 13, 17–24.

    Article  Google Scholar 

  74. Kalra, H., Simpson, R. J., Ji, H., Aikawa, E., Altevogt, P., Askenase, P., Bond, V. C., Borras, F. E., Breakefield, X., Budnik, V., Buzas, E., Camussi, G., Clayton, A., Cocucci, E., Falcon-Perez, J. M., Gabrielsson, S., Gho, Y. S., Gupta, D., Harsha, H. C., Hendrix, A., Hill, A. F., Inal, J. M., Jenster, G., Kramer-Albers, E. M., Lim, S. K., Llorente, A., Lotvall, J., Marcilla, A., Mincheva-Nilsson, L., Nazarenko, I., Nieuwland, R., Nolte’t-Hoen, E. N., Pandey, A., Patel, T., Piper, M. G., Pluchino, S., Prasad, T. S., Rajendran, L., Raposo, G., Record, M., Reid, G. E., Sanchez-Madrid, F., Schiffelers, R. M., Siljander, P., Stensballe, A., Stoorvogel, W., Taylor, D., Thery, C., Valadi, H., Van Balkom, B. W., Vazquez, J., Vidal, M., Wauben, M. H., Yanez-Mo, M., Zoeller, M., and Mathivanan, S. (2012) Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation, PLoS Biol., 10, e1001450.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Mathivanan, S., Fahner, C. J., Reid, G. E., and Simpson, R. J. (2012) ExoCarta 2012: database of exosomal proteins, RNA and lipids, Nucleic Acids Res., 40, 1241–1244.

    Article  Google Scholar 

  76. Zhang, C., Yao, C., Li, H., Wang, G., and He, X. (2014) Combined elevation of microRNA-196a and microRNA-196b in sera predicts unfavorable prognosis in patients with osteosarcomas, Int. J. Mol. Sci., 15, 6544–6555.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Yuan, J., Chen, L., Chen, X., Sun, W., and Zhou, X. (2012) Identification of serum microRNA-21 as a biomarker for chemosensitivity and prognosis in human osteosarcoma, J. Int. Med. Res., 40, 2090–2097.

    Article  CAS  PubMed  Google Scholar 

  78. Cai, H., Lin, L., Cai, H., Tang, M., and Wang, Z. (2013) Prognostic evaluation of microRNA-210 expression in pediatric osteosarcoma, Med. Oncol., 30, 499.

    Article  PubMed  Google Scholar 

  79. Sarver, A. L., Thayanithy, V., Scott, M. C., Cleton-Jansen, A. M., Hogendoorn, P. C., Modiano, J. F., and Subramanian, S. (2013) MicroRNAs at the human 14q32 locus have prognostic significance in osteosarcoma, Orphanet. J. Rare Dis., 8, 7.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Wang, Y., Jia, L. S., Yuan, W., Wu, Z., Wang, H. B., Xu, T., Sun, J. C., Cheng, K. F., and Shi, J. G. (2015) Low miR-34a and miR-192 are associated with unfavorable prognosis in patients suffering from osteosarcoma, Am. J. Trancl. Res., 7, 111–119.

    Google Scholar 

  81. Varshney, J., and Subramanian, S. (2015) MicroRNAs as potential target in human bone and soft tissue sarcoma therapeutics, Front. Mol. Biosci., 2, 31.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Chen, Y., Zhu, X., Zhang, X., Liu, B., and Huang, L. (2010) Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy, Mol. Ther., 18, 1650–1656.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Blokhin Cancer Research Center, 115478, Moscow, Russia

    N. E. Kushlinskii

  2. Vavilov Institute of General Genetics, Russian Academy of Sciences, 117971, Moscow, Russia

    M. V. Fridman

  3. Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia

    E. A. Braga

Authors
  1. N. E. Kushlinskii
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. V. Fridman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. A. Braga
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. A. Braga.

Additional information

Original Russian Text © N. E. Kushlinskii, M. V. Fridman, E. A. Braga, 2016, published in Biokhimiya, 2016, Vol. 81, No. 4, pp. 448-464.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kushlinskii, N.E., Fridman, M.V. & Braga, E.A. Molecular mechanisms and microRNAs in osteosarcoma pathogenesis. Biochemistry Moscow 81, 315–328 (2016). https://doi.org/10.1134/S0006297916040027

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297916040027

Keywords

Search

Navigation