Skip to main content

microRNA and Bone Cancer

  • Chapter
microRNA: Cancer

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

Abstract

MicroRNA molecules have a variety of roles in cellular development and proliferation processes, including normal osteogenesis. These effects are exerted through post-translational inhibition of target genes. Altered miRNA expression has been demonstrated in several cancers, both in the tumor tissue and in the peripheral circulation. This may influence carcinogenesis if the specific miRNA targets are encoded by tumor suppressor genes or oncogenes. To date, most research investigating the role of microRNAs and primary bone tumors has focused on osteosarcoma and Ewing sarcoma. Several microRNAs including the miR-34 family have been implicated in osteosarcoma tumorigenesis via effects on the Notch signaling pathway. Progression, invasion, and metastasis of osteosarcoma tumor cells is also influenced by microRNA expression. In addition, microRNA expression may affect the response to chemotherapy in osteosarcoma and thus hold potential for future use as either a prognostic indicator or a therapeutic target. The EWS-FLI1 fusion protein produced in Ewing sarcoma has been shown to induce changes in miRNA expression. MicroRNA expression profiling may have some potential for prediction of disease progression and survival in Ewing sarcoma. There is limited evidence to support a role for microRNAs in other primary bone tumors, either malignant or benign; however, early work is suggestive of involvement in chondrosarcoma, multiple osteochondromatosis, and giant cell tumors of bone.

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

Access this chapter

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. Ibrahim T, Mercatali L, Amadori D. Bone and cancer: the osteoncology. Clin Cases Miner Bone Metab. 2013;10(2):121–3.

    PubMed  PubMed Central  Google Scholar 

  2. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.

    Article  CAS  PubMed  Google Scholar 

  3. miRBase 21. Manchester: University of Manchester; 2014. http://www.mirbase.org/index.shtml. Accessed June 2014 to 22nd Dec 2014

  4. Griffiths-Jones S. The microRNA registry. Nucleic Acids Res. 2004;32(Database issue):D109–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Griffiths-Jones S. miRBase: the microRNA sequence database. Methods Mol Biol. 2006;342:129–38.

    CAS  PubMed  Google Scholar 

  6. Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 2006;34(Database issue):D140–4.

    Article  CAS  PubMed  Google Scholar 

  7. Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 2011;39(Database issue):D152–7.

    Google Scholar 

  8. Kozomara A, Griffiths-Jones S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 2014;42(Database issue):D68–73.

    Google Scholar 

  9. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5(7):522–31.

    Article  CAS  PubMed  Google Scholar 

  10. Valencia-Sanchez MA, Liu J, Hannon GJ, Parker R. Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 2006;20(5):515–24.

    Google Scholar 

  11. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.

    Article  CAS  PubMed  Google Scholar 

  12. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009;11(3):228–34.

    Google Scholar 

  13. Hammond SM, Caudy AA, Hannon GJ. Post-transcriptional gene silencing by double-stranded RNA. Nat Rev Genet. 2001;2(2):110–9.

    Article  CAS  PubMed  Google Scholar 

  14. Mirnezami AH, Pickard K, Zhang L, Primrose JN, Packham G. MicroRNAs: key players in carcinogenesis and novel therapeutic targets. Eur J Surg Oncol. 2009;35(4):339–47.

    Article  CAS  PubMed  Google Scholar 

  15. Nugent M. MicroRNA function and dysregulation in bone tumors: the evidence to date. Cancer Manag Res. 2014;6:15–25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Bae Y, Yang T, Zeng HC, Campeau PM, Chen Y, Bertin T, et al. miRNA-34c regulates Notch signaling during bone development. Hum Mol Genet. 2012;21(13):2991–3000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Krzeszinski JY, Wei W, Huynh H, Jin Z, Wang X, Chang TC, et al. miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2. Nature. 2014;512(7515):431–5.

    Article  CAS  PubMed  Google Scholar 

  18. Kim K, Kim JH, Kim I, Lee J, Seong S, Park YW, et al. MicroRNA-26a Regulates RANKL-Induced Osteoclast Formation. Mol Cells. 2015;38(1):75–80.

    CAS  PubMed  Google Scholar 

  19. Li Z, Hassan MQ, Volinia S, van Wijnen AJ, Stein JL, Croce CM, et al. A microRNA signature for a BMP2-induced osteoblast lineage commitment program. Proc Natl Acad Sci U S A. 2008;105(37):13906–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kureel J, Dixit M, Tyagi AM, Mansoori MN, Srivastava K, Raghuvanshi A, et al. miR-542-3p suppresses osteoblast cell proliferation and differentiation, targets BMP-7 signaling and inhibits bone formation. Cell Death Dis. 2014;5:e1050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Li S, Fu H, Wang Y, Tie Y, Xing R, Zhu J, et al. MicroRNA-101 regulates expression of the v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene in human hepatocellular carcinoma. Hepatology. 2009;49(4):1194–202.

    Article  CAS  PubMed  Google Scholar 

  22. Slaby O, Svoboda M, Michalek J, Vyzula R. MicroRNAs in colorectal cancer: translation of molecular biology into clinical application. Mol Cancer. 2009;8:102.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Rossi S, Kopetz S, Davuluri R, Hamilton SR, Calin GA. MicroRNAs, ultraconserved genes and colorectal cancers. Int J Biochem Cell Biol. 2010;42(8):1291–7.

    Article  CAS  PubMed  Google Scholar 

  24. Wijnhoven BP, Michael MZ, Watson DI. MicroRNAs and cancer. Br J Surg. 2007;94(1):23–30.

    Article  CAS  PubMed  Google Scholar 

  25. Kobayashi E, Hornicek FJ, Duan Z. MicroRNA involvement in osteosarcoma. Sarcoma. 2012;2012:359739.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res. 2009;152:3–13.

    Article  PubMed  Google Scholar 

  27. Tang N, Song WX, Luo J, Haydon RC, He TC. Osteosarcoma development and stem cell differentiation. Clin Orthop Relat Res. 2008;466(9):2114–30.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2002;20(3):776–90.

    Article  PubMed  Google Scholar 

  29. Geller DS, Gorlick R. Osteosarcoma: a review of diagnosis, management, and treatment strategies. Clin Adv Hematol Oncol. 2010;8(10):705–18.

    PubMed  Google Scholar 

  30. Wang Z, Li Y, Banerjee S, Sarkar FH. Emerging role of Notch in stem cells and cancer. Cancer Lett. 2009;279(1):8–12.

    Article  CAS  PubMed  Google Scholar 

  31. Wang Z, Li Y, Kong D, Ahmad A, Banerjee S, Sarkar FH. Cross-talk between miRNA and Notch signaling pathways in tumor development and progression. Cancer Lett. 2010;292(2):141–8.

    Article  CAS  PubMed  Google Scholar 

  32. He C, Xiong J, Xu X, Lu W, Liu L, Xiao D, et al. Functional elucidation of MiR-34 in osteosarcoma cells and primary tumor samples. Biochem Biophys Res Commun. 2009;388(1):35–40.

    Article  CAS  PubMed  Google Scholar 

  33. He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447(7148):1130–4.

    Google Scholar 

  34. Li J, Liu W, Zhao K, Zhang Y, Li X, Yang Q, et al. Diallyl trisulfide reverses drug resistance and lowers the ratio of CD133+ cells in conjunction with methotrexate in a human osteosarcoma drug-resistant cell subline. Mol Med Rep. 2009;2(2):245–52.

    Google Scholar 

  35. Li Y, Zhang J, Zhang L, Si M, Yin H, Li J. Diallyl trisulfide inhibits proliferation, invasion and angiogenesis of osteosarcoma cells by switching on suppressor microRNAs and inactivating of Notch-1 signaling. Carcinogenesis. 2013;34(7):1601–10.

    Article  CAS  PubMed  Google Scholar 

  36. Song L, Yang J, Duan P, Xu J, Luo X, Luo F, et al. MicroRNA-24 inhibits osteosarcoma cell proliferation both in vitro and in vivo by targeting LPAATbeta. Arch Biochem Biophys. 2013;535(2):128–35.

    Google Scholar 

  37. Annunziata M, Granata R, Ghigo E. The IGF system. Acta Diabetol. 2011;48(1):1–9.

    Google Scholar 

  38. Chen L, Wang Q, Wang GD, Wang HS, Huang Y, Liu XM, et al. miR-16 inhibits cell proliferation by targeting IGF1R and the Raf1-MEK1/2-ERK1/2 pathway in osteosarcoma. FEBS Lett. 2013;587(9):1366–72.

    Article  CAS  PubMed  Google Scholar 

  39. Maire G, Martin JW, Yoshimoto M, Chilton-MacNeill S, Zielenska M, Squire JA. Analysis of miRNA-gene expression-genomic profiles reveals complex mechanisms of microRNA deregulation in osteosarcoma. Cancer Genet. 2011;204(3):138–46.

    Article  CAS  PubMed  Google Scholar 

  40. Thayanithy V, Sarver AL, Kartha RV, Li L, Angstadt AY, Breen M, et al. Perturbation of 14q32 miRNAs-cMYC gene network in osteosarcoma. Bone. 2012;50(1):171–81.

    Article  CAS  PubMed  Google Scholar 

  41. Xiang J, Wu J. Feud or friend? The role of the miR-17-92 cluster in tumorigenesis. Curr Genomics. 2010;11(2):129–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhou M, Ma J, Chen S, Chen X, Yu X. MicroRNA-17-92 cluster regulates osteoblast proliferation and differentiation. Endocrine. 2014;45(2):302–10.

    Article  CAS  PubMed  Google Scholar 

  43. Arabi L, Gsponer JR, Smida J, Nathrath M, Perrina V, Jundt G, et al. Upregulation of the miR-17-92 cluster and its two paraloga in osteosarcoma—reasons and consequences. Genes Cancer. 2014;5(1–2):56–63.

    PubMed  PubMed Central  Google Scholar 

  44. Xu SH, Yang YL, Han SM, Wu ZH. MicroRNA-9 expression is a prognostic biomarker in patients with osteosarcoma. World J Surg Oncol. 2014;12:195.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ziyan W, Shuhua Y, Xiufang W, Xiaoyun L. MicroRNA-21 is involved in osteosarcoma cell invasion and migration. Med Oncol. 2011;28(4):1469–74.

    Article  PubMed  CAS  Google Scholar 

  46. Ouyang L, Liu P, Yang S, Ye S, Xu W, Liu X. A three-plasma miRNA signature serves as novel biomarkers for osteosarcoma. Med Oncol. 2013;30(1):340.

    Article  PubMed  CAS  Google Scholar 

  47. Montanini L, Lasagna L, Barili V, Jonstrup SP, Murgia A, Pazzaglia L, et al. MicroRNA cloning and sequencing in osteosarcoma cell lines: differential role of miR-93. Cell Oncol (Dordr). 2012;35(1):29–41.

    Article  CAS  Google Scholar 

  48. Tian Z, Guo B, Yu M, Wang C, Zhang H, Liang Q, et al. Upregulation of micro-ribonucleic acid-128 cooperating with downregulation of PTEN confers metastatic potential and unfavorable prognosis in patients with primary osteosarcoma. Onco Targets Ther. 2014;7:1601–8.

    PubMed  PubMed Central  Google Scholar 

  49. Lauvrak SU, Munthe E, Kresse SH, Stratford EW, Namlos HM, Meza-Zepeda LA, et al. Functional characterisation of osteosarcoma cell lines and identification of mRNAs and miRNAs associated with aggressive cancer phenotypes. Br J Cancer. 2013;109(8):2228–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lulla RR, Costa FF, Bischof JM, Chou PM, de F Bonaldo M, Vanin EF, et al. Identification of differentially expressed microRNAs in osteosarcoma. Sarcoma. 2011;2011:732690.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Jones KB, Salah Z, Del Mare S, Galasso M, Gaudio E, Nuovo GJ, et al. miRNA signatures associate with pathogenesis and progression of osteosarcoma. Cancer Res. 2012;72(7):1865–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Won KY, Kim YW, Kim HS, Lee SK, Jung WW, Park YK. MicroRNA-199b-5p is involved in the Notch signaling pathway in osteosarcoma. Hum Pathol. 2013;44(8):1648–55.

    Article  CAS  PubMed  Google Scholar 

  53. Cai H, Lin L, Tang M, Wang Z. Prognostic evaluation of microRNA-210 expression in pediatric osteosarcoma. Med Oncol. 2013;30(2):499.

    Article  PubMed  CAS  Google Scholar 

  54. Xu Z, Wang T. miR-214 promotes the proliferation and invasion of osteosarcoma cells through direct suppression of LZTS1. Biochem Biophys Res Commun. 2014;449(2):190–5.

    Article  CAS  PubMed  Google Scholar 

  55. Zhao G, Cai C, Yang T, Qiu X, Liao B, Li W, et al. MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PLoS One. 2013;8(1):e53906.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhang W, Qian JX, Yi HL, Yang ZD, Wang CF, Chen JY, et al. The microRNA-29 plays a central role in osteosarcoma pathogenesis and progression. Mol Biol (Mosk). 2012;46(4):622–7.

    CAS  Google Scholar 

  57. Zhang K, Zhang C, Liu L, Zhou J. A key role of microRNA-29b in suppression of osteosarcoma cell proliferation and migration via modulation of VEGF. Int J Clin Exp Pathol. 2014;7(9):5701–8.

    PubMed  PubMed Central  Google Scholar 

  58. Baglio SR, Devescovi V, Granchi D, Baldini N. MicroRNA expression profiling of human bone marrow mesenchymal stem cells during osteogenic differentiation reveals Osterix regulation by miR-31. Gene. 2013;527(1):321–31.

    Article  CAS  PubMed  Google Scholar 

  59. Tian Y, Zhang YZ, Chen W. MicroRNA-199a-3p and microRNA-34a regulate apoptosis in human osteosarcoma cells. Biosci Rep. 2014;34(4).

    Google Scholar 

  60. Yan K, Gao J, Yang T, Ma Q, Qiu X, Fan Q, et al. MicroRNA-34a inhibits the proliferation and metastasis of osteosarcoma cells both in vitro and in vivo. PLoS One. 2012;7(3):e33778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Tian Q, Jia J, Ling S, Liu Y, Yang S, Shao Z. A causal role for circulating miR-34b in osteosarcoma. Eur J Surg Oncol. 2014;40(1):67–72.

    Article  CAS  PubMed  Google Scholar 

  62. van der Deen M, Taipaleenmaki H, Zhang Y, Teplyuk NM, Gupta A, Cinghu S, et al. MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma. J Biol Chem. 2013;288(29):21307–19.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Lin S, Shao NN, Fan L, Ma XC, Pu FF, Shao ZW. Effect of microRNA-101 on proliferation and apoptosis of human osteosarcoma cells by targeting mTOR. J Huazhong Univ Sci Technolog Med Sci. 2014;34(6):889–95.

    Article  CAS  PubMed  Google Scholar 

  64. Liu LH, Li H, Li JP, Zhong H, Zhang HC, Chen J, et al. miR-125b suppresses the proliferation and migration of osteosarcoma cells through down-regulation of STAT3. Biochem Biophys Res Commun. 2011;416(1–2):31–8.

    Article  CAS  PubMed  Google Scholar 

  65. Yang C, Hou C, Zhang H, Wang D, Ma Y, Zhang Y, et al. miR-126 functions as a tumor suppressor in osteosarcoma by targeting Sox2. Int J Mol Sci. 2014;15(1):423–37.

    Article  CAS  Google Scholar 

  66. Yang J, Zhang W. New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol. 2013;25(4):398–406.

    Article  CAS  PubMed  Google Scholar 

  67. Yang J, Gao T, Tang J, Cai H, Lin L, Fu S. Loss of microRNA-132 predicts poor prognosis in patients with primary osteosarcoma. Mol Cell Biochem. 2013;381(1–2):9–15.

    Article  CAS  PubMed  Google Scholar 

  68. Ji F, Zhang H, Wang Y, Li M, Xu W, Kang Y, et al. MicroRNA-133a, downregulated in osteosarcoma, suppresses proliferation and promotes apoptosis by targeting Bcl-xL and Mcl-1. Bone. 2013;56(1):220–6.

    Article  CAS  PubMed  Google Scholar 

  69. Zhao H, Li M, Li L, Yang X, Lan G, Zhang Y. MiR-133b is down-regulated in human osteosarcoma and inhibits osteosarcoma cells proliferation, migration and invasion, and promotes apoptosis. PLoS One. 2013;8(12):e83571.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Liu Z, Zhang G, Li J, Liu J, Lv P. The tumor-suppressive microRNA-135b targets c-myc in osteosarcoma. PLoS One. 2014;9(7):e102621.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Tang M, Lin L, Cai H, Tang J, Zhou Z. MicroRNA-145 downregulation associates with advanced tumor progression and poor prognosis in patients suffering osteosarcoma. Onco Targets Ther. 2013;6:833–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Zhu J, Feng Y, Ke Z, Yang Z, Zhou J, Huang X, et al. Down-regulation of miR-183 promotes migration and invasion of osteosarcoma by targeting Ezrin. Am J Pathol. 2012;180(6):2440–51.

    Article  CAS  PubMed  Google Scholar 

  73. Duan Z, Choy E, Harmon D, Liu X, Susa M, Mankin H, et al. MicroRNA-199a-3p is downregulated in human osteosarcoma and regulates cell proliferation and migration. Mol Cancer Ther. 2011;10(8):1337–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Bao YP, Yi Y, Peng LL, Fang J, Liu KB, Li WZ, et al. Roles of microRNA-206 in osteosarcoma pathogenesis and progression. Asian Pac J Cancer Prev. 2013;14(6):3751–5.

    Article  PubMed  Google Scholar 

  75. Zhang H, Yin Z, Ning K, Wang L, Guo R, Ji Z. Prognostic value of microRNA-223/epithelial cell transforming sequence 2 signaling in patients with osteosarcoma. Hum Pathol. 2014;45(7):1430–6.

    Article  CAS  PubMed  Google Scholar 

  76. Cheng C, Chen ZQ, Shi XT. MicroRNA-320 inhibits osteosarcoma cells proliferation by directly targeting fatty acid synthase. Tumour Biol. 2014;35(5):4177–83.

    Article  CAS  PubMed  Google Scholar 

  77. Wang Y, Zhao W, Fu Q. miR-335 suppresses migration and invasion by targeting ROCK1 in osteosarcoma cells. Mol Cell Biochem. 2013;384(1–2):105–11.

    Article  CAS  PubMed  Google Scholar 

  78. Zhou X, Wei M, Wang W. MicroRNA-340 suppresses osteosarcoma tumor growth and metastasis by directly targeting ROCK1. Biochem Biophys Res Commun. 2013;437(4):653–8.

    Article  CAS  PubMed  Google Scholar 

  79. Long XH, Mao JH, Peng AF, Zhou Y, Huang SH, Liu ZL. Tumor suppressive microRNA-424 inhibits osteosarcoma cell migration and invasion via targeting fatty acid synthase. Exp Ther Med. 2013;5(4):1048–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Yuan J, Lang J, Liu C, Zhou K, Chen L, Liu Y. The expression and function of miRNA-451 in osteosarcoma. Med Oncol. 2015;32(1):324.

    Article  PubMed  CAS  Google Scholar 

  81. Kager L, Zoubek A, Potschger U, Kastner U, Flege S, Kempf-Bielack B, et al. Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol. 2003;21(10):2011–8.

    Article  PubMed  Google Scholar 

  82. Kempf-Bielack B, Bielack SS, Jurgens H, Branscheid D, Berdel WE, Exner GU, et al. Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol. 2005;23(3):559–68.

    Article  PubMed  Google Scholar 

  83. Bacci G, Rocca M, Salone M, Balladelli A, Ferrari S, Palmerini E, et al. High grade osteosarcoma of the extremities with lung metastases at presentation: treatment with neoadjuvant chemotherapy and simultaneous resection of primary and metastatic lesions. J Surg Oncol. 2008;98(6):415–20.

    Article  PubMed  Google Scholar 

  84. Lafleur EA, Koshkina NV, Stewart J, Jia SF, Worth LL, Duan X, et al. Increased Fas expression reduces the metastatic potential of human osteosarcoma cells. Clin Cancer Res. 2004;10(23):8114–9.

    Article  CAS  PubMed  Google Scholar 

  85. Worth LL, Lafleur EA, Jia SF, Kleinerman ES. Fas expression inversely correlates with metastatic potential in osteosarcoma cells. Oncol Rep. 2002;9(4):823–7.

    CAS  PubMed  Google Scholar 

  86. Huang G, Nishimoto K, Zhou Z, Hughes D, Kleinerman ES. miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating Fas expression. Cancer Res. 2012;72(4):908–16.

    Article  CAS  PubMed  Google Scholar 

  87. Osaki M, Takeshita F, Sugimoto Y, Kosaka N, Yamamoto Y, Yoshioka Y, et al. MicroRNA-143 regulates human osteosarcoma metastasis by regulating matrix metalloprotease-13 expression. Mol Ther. 2011;19(6):1123–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Schofield AV, Bernard O. Rho-associated coiled-coil kinase (ROCK) signaling and disease. Crit Rev Biochem Mol Biol. 2013;48(4):301–16.

    Article  CAS  PubMed  Google Scholar 

  89. Lei P, Xie J, Wang L, Yang X, Dai Z, Hu Y. microRNA-145 inhibits osteosarcoma cell proliferation and invasion by targeting ROCK1. Mol Med Rep. 2014;10(1):155–60.

    CAS  PubMed  Google Scholar 

  90. Cai H, Lin L, Tang M, Wang Z. Combined microRNA-340 and ROCK1 mRNA profiling predicts tumor progression and prognosis in pediatric osteosarcoma. Int J Mol Sci. 2014;15(1):560–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Song QC, Shi ZB, Zhang YT, Ji L, Wang KZ, Duan DP, et al. Downregulation of microRNA-26a is associated with metastatic potential and the poor prognosis of osteosarcoma patients. Oncol Rep. 2014;31(3):1263–70.

    CAS  PubMed  Google Scholar 

  92. Simon JA, Lange CA. Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutat Res. 2008;647(1–2):21–9.

    Article  CAS  PubMed  Google Scholar 

  93. Pan W, Wang H, Jianwei R, Ye Z. MicroRNA-27a promotes proliferation, migration and invasion by targeting MAP2K4 in human osteosarcoma cells. Cell Physiol Biochem. 2014;33(2):402–12.

    Article  CAS  PubMed  Google Scholar 

  94. Lv H, Pei J, Liu H, Wang H, Liu J. A polymorphism site in the premiR34a coding region reduces miR34a expression and promotes osteosarcoma cell proliferation and migration. Mol Med Rep. 2014;10(6):2912–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Wang J, Xu G, Shen F, Kang Y. miR-132 targeting cyclin E1 suppresses cell proliferation in osteosarcoma cells. Tumour Biol. 2014;35(5):4859–65.

    Article  CAS  PubMed  Google Scholar 

  96. Zhao M, Huang J, Gui K, Xiong M, Cai G, Xu J, et al. The downregulation of miR-144 is associated with the growth and invasion of osteosarcoma cells through the regulation of TAGLN expression. Int J Mol Med. 2014;34(6):1565–72.

    CAS  PubMed  Google Scholar 

  97. Zhao H, Guo M, Zhao G, Ma Q, Ma B, Qiu X, et al. miR-183 inhibits the metastasis of osteosarcoma via downregulation of the expression of Ezrin in F5M2 cells. Int J Mol Med. 2012;30(5):1013–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Shen L, Wang P, Yang J, Li X. MicroRNA-217 regulates WASF3 expression and suppresses tumor growth and metastasis in osteosarcoma. PLoS One. 2014;9(10):e109138.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Suetsugu S, Takenawa T. Regulation of cortical actin networks in cell migration. Int Rev Cytol. 2003;229:245–86.

    Article  CAS  PubMed  Google Scholar 

  100. Wang Z, Cai H, Lin L, Tang M. Upregulated expression of microRNA-214 is linked to tumor progression and adverse prognosis in pediatric osteosarcoma. Pediatr Blood Cancer. 2014;61(2):206–10.

    Article  PubMed  Google Scholar 

  101. Wang X, Sun J, Fu C, Wang D, Bi Z. MicroRNA-214 regulates osteosarcoma survival and growth by directly targeting phosphatase and tensin homolog. Mol Med Rep. 2014;10(6):3073–9.

    CAS  PubMed  Google Scholar 

  102. Gougelet A, Pissaloux D, Besse A, Perez J, Duc A, Dutour A, et al. Micro-RNA profiles in osteosarcoma as a predictive tool for ifosfamide response. Int J Cancer. 2011;129(3):680–90.

    Article  CAS  PubMed  Google Scholar 

  103. Song B, Wang Y, Xi Y, Kudo K, Bruheim S, Botchkina GI, et al. Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells. Oncogene. 2009;28(46):4065–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Guo S, Bai R, Liu W, Zhao A, Zhao Z, Wang Y, et al. miR-22 inhibits osteosarcoma cell proliferation and migration by targeting HMGB1 and inhibiting HMGB1-mediated autophagy. Tumour Biol. 2014;35(7):7025–34.

    Article  CAS  PubMed  Google Scholar 

  105. Entz-Werle N, Lavaux T, Metzger N, Stoetzel C, Lasthaus C, Marec P, et al. Involvement of MET/TWIST/APC combination or the potential role of ossification factors in pediatric high-grade osteosarcoma oncogenesis. Neoplasia. 2007;9(8):678–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Zhou Y, Zang X, Huang Z, Zhang C. TWIST interacts with endothelin-1/endothelin A receptor signaling in osteosarcoma cell survival against cisplatin. Oncol Lett. 2013;5(3):857–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Wu J, Liao Q, He H, Zhong D, Yin K. TWIST interacts with beta-catenin signaling on osteosarcoma cell survival against cisplatin. Mol Carcinog. 2014;53(6):440–6.

    Article  CAS  PubMed  Google Scholar 

  108. Zhou Y, Huang Z, Wu S, Zang X, Liu M, Shi J. miR-33a is up-regulated in chemoresistant osteosarcoma and promotes osteosarcoma cell resistance to cisplatin by down-regulating TWIST. J Exp Clin Cancer Res. 2014;33:12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Mu Y, Zhang H, Che L, Li K. Clinical significance of microRNA-183/Ezrin axis in judging the prognosis of patients with osteosarcoma. Med Oncol. 2014;31(2):821.

    Article  PubMed  CAS  Google Scholar 

  110. Sarver AL, Thayanithy V, Scott MC, Cleton-Jansen AM, Hogendoorn PC, Modiano JF, et al. MicroRNAs at the human 14q32 locus have prognostic significance in osteosarcoma. Orphanet J Rare Dis. 2013;8:7.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Kelly AD, Haibe-Kains B, Janeway KA, Hill KE, Howe E, Goldsmith J, et al. MicroRNA paraffin-based studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32. Genome Med. 2013;5(1):2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Nakatani F, Ferracin M, Manara MC, Ventura S, Del Monaco V, Ferrari S, et al. miR-34a predicts survival of Ewing’s sarcoma patients and directly influences cell chemo-sensitivity and malignancy. J Pathol. 2012;226(5):796–805.

    Article  CAS  PubMed  Google Scholar 

  113. Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Kerin MJ. Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg. 2010;251(3):499–505.

    Article  PubMed  Google Scholar 

  114. Nugent M, Miller N, Kerin MJ. Circulating miR-34a levels are reduced in colorectal cancer. J Surg Oncol. 2012;106(8):947–52.

    Article  CAS  PubMed  Google Scholar 

  115. 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 

  116. 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 

  117. Yuan J, Chen L, Chen X, Sun W, Zhou X. Identification of serum microRNA-21 as a biomarker for chemosensitivity and prognosis in human osteosarcoma. J Int Med Res. 2012;40(6):2090–7.

    Article  CAS  PubMed  Google Scholar 

  118. Zhang C, Yao C, Li H, Wang G, He X. Combined elevation of microRNA-196a and microRNA-196b in sera predicts unfavorable prognosis in patients with osteosarcomas. Int J Mol Sci. 2014;15(4):6544–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Zhang C, Yao C, Li H, Wang G, He X. Serum levels of microRNA-133b and microRNA-206 expression predict prognosis in patients with osteosarcoma. Int J Clin Exp Pathol. 2014;7(7):4194–203.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Stahl M, Ranft A, Paulussen M, Bolling T, Vieth V, Bielack S, et al. Risk of recurrence and survival after relapse in patients with Ewing sarcoma. Pediatr Blood Cancer. 2011;57(4):549–53.

    Article  PubMed  Google Scholar 

  121. Schwab JH, Springfield DS, Raskin KA, Mankin HJ, Hornicek FJ. What’s new in primary bone tumors. J Bone Joint Surg Am. 2012;94(20):1913–9.

    Article  PubMed  Google Scholar 

  122. Sorensen PH, Lessnick SL, Lopez-Terrada D, Liu XF, Triche TJ, Denny CT. A second Ewing’s sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor. ERG Nat Genet. 1994;6(2):146–51.

    Article  CAS  PubMed  Google Scholar 

  123. Jeon IS, Davis JN, Braun BS, Sublett JE, Roussel MF, Denny CT, et al. A variant Ewing’s sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene. 1995;10(6):1229–34.

    CAS  PubMed  Google Scholar 

  124. Riggi N, Stamenkovic I. The biology of Ewing sarcoma. Cancer Lett. 2007;254(1):1–10.

    Article  CAS  PubMed  Google Scholar 

  125. Kovar H. Downstream EWS/FLI1—upstream Ewing’s sarcoma. Genome Med. 2010;2(1):8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Kinsey M, Smith R, Iyer AK, McCabe ER, Lessnick SL. EWS/FLI and its downstream target NR0B1 interact directly to modulate transcription and oncogenesis in Ewing’s sarcoma. Cancer Res. 2009;69(23):9047–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. De Vito C, Riggi N, Suva ML, Janiszewska M, Horlbeck J, Baumer K, et al. Let-7a is a direct EWS-FLI-1 target implicated in Ewing’s sarcoma development. PLoS One. 2011;6(8):e23592.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Parrish JK, Sechler M, Winn RA, Jedlicka P. The histone demethylase KDM3A is a microRNA-22-regulated tumor promoter in Ewing Sarcoma. Oncogene. 2013;34(2):257–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  129. Karnuth B, Dedy N, Spieker T, Lawlor ER, Gattenlohner S, Ranft A, et al. Differentially expressed miRNAs in Ewing sarcoma compared to mesenchymal stem cells: low miR-31 expression with effects on proliferation and invasion. PLoS One. 2014;9(3):e93067.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Marino MT, Grilli A, Baricordi C, Manara MC, Ventura S, Pinca RS, et al. Prognostic significance of miR-34a in Ewing sarcoma is associated with cyclin D1 and ki-67 expression. Ann Oncol. 2014;25(10):2080–6.

    Article  CAS  PubMed  Google Scholar 

  131. Pestell RG. New roles of cyclin D1. Am J Pathol. 2013;183(1):3–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Li J, You T, Jing J. MiR-125b inhibits cell biological progression of Ewing’s sarcoma by suppressing the PI3K/Akt signalling pathway. Cell Prolif. 2014;47(2):152–60.

    Article  CAS  PubMed  Google Scholar 

  133. Ban J, Jug G, Mestdagh P, Schwentner R, Kauer M, Aryee DN, et al. Hsa-mir-145 is the top EWS-FLI1-repressed microRNA involved in a positive feedback loop in Ewing’s sarcoma. Oncogene. 2011;30(18):2173–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Robin TP, Smith A, McKinsey E, Reaves L, Jedlicka P, Ford HL. EWS/FLI1 regulates EYA3 in Ewing sarcoma via modulation of miRNA-708, resulting in increased cell survival and chemoresistance. Mol Cancer Res. 2012;10(8):1098–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Franzetti GA, Laud-Duval K, Bellanger D, Stern MH, Sastre-Garau X, Delattre O. MiR-30a-5p connects EWS-FLI1 and CD99, two major therapeutic targets in Ewing tumor. Oncogene. 2013;32(33):3915–21.

    Article  CAS  PubMed  Google Scholar 

  136. Riggi N, Suva ML, De Vito C, Provero P, Stehle JC, Baumer K, et al. EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells. Genes Dev. 2010;24(9):916–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. David E, Blanchard F, Heymann MF, De Pinieux G, Gouin F, Redini F, et al. The bone niche of chondrosarcoma: a sanctuary for drug resistance, tumour growth and also a source of new therapeutic targets. Sarcoma. 2011;2011:932451.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Onishi AC, Hincker AM, Lee FY. Surmounting chemotherapy and radioresistance in chondrosarcoma: molecular mechanisms and therapeutic targets. Sarcoma. 2011;2011:381564.

    Article  PubMed  Google Scholar 

  139. Yoshitaka T, Kawai A, Miyaki S, Numoto K, Kikuta K, Ozaki T, et al. Analysis of microRNAs expressions in chondrosarcoma. J Orthop Res. 2013;31(12):1992–8.

    Article  CAS  PubMed  Google Scholar 

  140. Zhu Z, Wang CP, Zhang YF, Nie L. MicroRNA-100 resensitizes resistant chondrosarcoma cells to cisplatin through direct targeting of mTOR. Asian Pac J Cancer Prev. 2014;15(2):917–23.

    Article  PubMed  Google Scholar 

  141. Liu G, Huang Y, Tzeng H, Tsai C, Wang S, Tang C. CCL5 promotes vascular endothelial growth factor expression and induces angiogenesis by down-regulating miR-199a in human chondrosarcoma cells. Cancer Lett. 2014;357(2):476–87.

    Article  PubMed  CAS  Google Scholar 

  142. Liang W, Li X, Li Y, Li C, Gao B, Gan H, et al. Gallic acid induces apoptosis and inhibits cell migration by upregulating miR-518b in SW1353 human chondrosarcoma cells. Int J Oncol. 2014;44(1):91–8.

    CAS  PubMed  Google Scholar 

  143. Galoian KA, Guettouche T, Issac B, Qureshi A, Temple HT. Regulation of onco and tumor suppressor MiRNAs by mTORC1 inhibitor PRP-1 in human chondrosarcoma. Tumour Biol. 2013;35(3):2335–41.

    Article  PubMed  CAS  Google Scholar 

  144. Schmale GA, Conrad 3rd EU, Raskind WH. The natural history of hereditary multiple exostoses. J Bone Joint Surg Am. 1994;76(7):986–92.

    Article  CAS  PubMed  Google Scholar 

  145. Zuntini M, Salvatore M, Pedrini E, Parra A, Sgariglia F, Magrelli A, et al. MicroRNA profiling of multiple osteochondromas: identification of disease-specific and normal cartilage signatures. Clin Genet. 2010;78(6):507–16.

    Article  CAS  PubMed  Google Scholar 

  146. Raskin KA, Schwab JH, Mankin HJ, Springfield DS, Hornicek FJ. Giant cell tumor of bone. J Am Acad Orthop Surg. 2013;21(2):118–26.

    Article  PubMed  Google Scholar 

  147. Ghert M, Simunovic N, Cowan RW, Colterjohn N, Singh G. Properties of the stromal cell in giant cell tumor of bone. Clin Orthop Relat Res. 2007;459:8–13.

    Article  PubMed  Google Scholar 

  148. Cowan RW, Mak IW, Colterjohn N, Singh G, Ghert M. Collagenase expression and activity in the stromal cells from giant cell tumour of bone. Bone. 2009;44(5):865–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Mak IW, Cowan RW, Popovic S, Colterjohn N, Singh G, Ghert M. Upregulation of MMP-13 via Runx2 in the stromal cell of giant cell tumor of bone. Bone. 2009;45(2):377–86.

    Article  CAS  PubMed  Google Scholar 

  150. Mosakhani N, Pazzaglia L, Benassi MS, Borze I, Quattrini I, Picci P, et al. MicroRNA expression profiles in metastatic and non-metastatic giant cell tumor of bone. Histol Histopathol. 2013;28(5):671–8.

    PubMed  Google Scholar 

  151. Wu Z, Yin H, Liu T, Yan W, Li Z, Chen J, et al. MiR-126-5p regulates osteoclast differentiation and bone resorption in giant cell tumor through inhibition of MMP-13. Biochem Biophys Res Commun. 2014;443(3):944–9.

    Article  CAS  PubMed  Google Scholar 

  152. Lehner B, Kunz P, Saehr H, Fellenberg J. Epigenetic silencing of genes and microRNAs within the imprinted Dlk1-Dio3 region at human chromosome 14.32 in giant cell tumor of bone. BMC Cancer. 2014;14:495.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  153. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449(7163):682–8.

    Article  CAS  PubMed  Google Scholar 

  154. Lujambio A, Calin GA, Villanueva A, Ropero S, Sanchez-Cespedes M, Blanco D, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci U S A. 2008;105(36):13556–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Huang L, Dai T, Lin X, Zhao X, Chen X, Wang C, et al. MicroRNA-224 targets RKIP to control cell invasion and expression of metastasis genes in human breast cancer cells. Biochem Biophys Res Commun. 2012;425(2):127–33.

    Article  CAS  PubMed  Google Scholar 

  156. Gong M, Ma J, Guillemette R, Zhou M, Yang Y, Hock JM, et al. miR-335 inhibits small cell lung cancer bone metastases via IGF-1R and RANKL pathways. Mol Cancer Res. 2014;12(1):101–10.

    Article  CAS  PubMed  Google Scholar 

  157. Kuo PL, Liao SH, Hung JY, Huang MS, Hsu YL. MicroRNA-33a functions as a bone metastasis suppressor in lung cancer by targeting parathyroid hormone related protein. Biochim Biophys Acta. 2013;1830(6):3756–66.

    Article  CAS  PubMed  Google Scholar 

  158. Guo W, Ren D, Chen X, Tu X, Huang S, Wang M, et al. HEF1 promotes epithelial mesenchymal transition and bone invasion in prostate cancer under the regulation of microRNA-145. J Cell Biochem. 2013;114(7):1606–15.

    Article  CAS  PubMed  Google Scholar 

  159. Peng X, Guo W, Liu T, Wang X, Tu X, Xiong D, et al. Identification of miRs-143 and -145 that is associated with bone metastasis of prostate cancer and involved in the regulation of EMT. PLoS One. 2011;6(5):e20341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Saini S, Majid S, Yamamura S, Tabatabai L, Suh SO, Shahryari V, et al. Regulatory role of mir-203 in prostate cancer progression and metastasis. Clin Cancer Res. 2011;17(16):5287–98.

    Article  CAS  PubMed  Google Scholar 

  161. Viticchie G, Lena AM, Latina A, Formosa A, Gregersen LH, Lund AH, et al. MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines. Cell Cycle. 2011;10(7):1121–31.

    Article  CAS  PubMed  Google Scholar 

  162. Meng W, McElroy JP, Volinia S, Palatini J, Warner S, Ayers LW, et al. Comparison of microRNA deep sequencing of matched formalin-fixed paraffin-embedded and fresh frozen cancer tissues. PLoS One. 2013;8(5):e64393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Xiao F, Chen J, Lian C, Han P, Zhang C. Tumor necrosis factor related apoptosis inducing ligand induces cytotoxicity specific to osteosarcoma by microRNA response elements. Mol Med Rep. 2015;11(1):739–45.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mary Nugent .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Nugent, M. (2015). microRNA and Bone 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_11

Download citation

Publish with us

Policies and ethics