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Medical Oncology

, 32:172 | Cite as

Review of microRNA in osteosarcoma and chondrosarcoma

  • Le Chang
  • Swati Shrestha
  • Greg LaChaud
  • Michelle A. Scott
  • Aaron W. JamesEmail author
Review Article

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs, which play a complex role in posttranscriptional gene expression and can theoretically be used as a diagnostic or prognostic tool, or therapeutic target for neoplasia. Despite advances in the diagnosis and treatment of skeletal sarcomas, including osteosarcoma and chondrosarcoma, much remains unknown regarding their underpinning molecular mechanisms. Given the recent increasing knowledge base of miRNA roles in neoplasia, both as oncogenes and tumor suppressor genes, this review will focus on the available literature regarding the expression profiles and potential roles of miRNA in skeletal sarcomas. Although this is an emerging field, miRNA profiling may be of use in clarifying competing diagnoses of skeletal sarcomas and possibly indicate patient risk of resistance to traditional chemotherapeutic agents. While detecting and targeting miRNAs is currently limited to experimental investigations, miRNA may be utilized for future clinical management of skeletal sarcomas.

Keywords

Osteosarcoma Chondrosarcoma microRNA miRNA Skeletal sarcoma Oncogene Tumor suppressor 

Notes

Acknowledgments

The present work was supported by the UCLA Department of Pathology and Laboratory Medicine, the Translational Research Fund and the UCLA Daljit S. and Elaine Sarkaria Fellowship award. The authors thank the staff of UCLA Translational Pathology Core Laboratory and A.S. James for their excellent technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Lovat F, Valeri N, Croce CM. MicroRNAs in the pathogenesis of cancer. Semin Oncol. 2011;38(6):724–33.CrossRefPubMedGoogle Scholar
  2. 2.
    Yates LA, Norbury CJ, Gilbert RJ. The long and short of microRNA. Cell. 2013;153(3):516–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Sassen S, Miska EA, Caldas C. MicroRNA: implications for cancer. Virchows Arch. 2008;452(1):1–10.CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Mishra PJ, Merlino G. MicroRNA reexpression as differentiation therapy in cancer. J Clin Invest. 2009;119(8):2119–23.PubMedCentralPubMedGoogle Scholar
  5. 5.
    Mishra PJ. The miRNA-drug resistance connection: a new era of personalized medicine using noncoding RNA begins. Pharmacogenomics. 2012;13(12):1321–4.CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res. 2009;152:3–13.PubMedGoogle Scholar
  7. 7.
    Rytting M, et al. Osteosarcoma in preadolescent patients. Clin Orthop Relat Res. 2000;373:39–50.CrossRefPubMedGoogle Scholar
  8. 8.
    Ferguson WS, Goorin AM. Current treatment of osteosarcoma. Cancer Invest. 2001;19(3):292–315.CrossRefPubMedGoogle Scholar
  9. 9.
    Levine AJ, Hu W, Feng Z. The P53 pathway: what questions remain to be explored? Cell Death Differ. 2006;13(6):1027–36.CrossRefPubMedGoogle Scholar
  10. 10.
    Lau CC, et al. Frequent amplification and rearrangement of chromosomal bands 6p12-p21 and 17p11.2 in osteosarcoma. Genes Chromosomes Cancer. 2004;39(1):11–21.CrossRefPubMedGoogle Scholar
  11. 11.
    Ognjanovic S, et al. Sarcomas in TP53 germline mutation carriers: a review of the IARC TP53 database. Cancer. 2012;118(5):1387–96.CrossRefPubMedGoogle Scholar
  12. 12.
    Tsuchiya T, et al. Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic implications in osteosarcoma and Ewing sarcoma. Cancer Genet Cytogenet. 2000;120(2):91–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Jacks T, et al. Tumor spectrum analysis in p53-mutant mice. Curr Biol. 1994;4(1):1–7.CrossRefPubMedGoogle Scholar
  14. 14.
    He L, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447(7148):1130–4.CrossRefPubMedGoogle Scholar
  15. 15.
    Hermeking H. The miR-34 family in cancer and apoptosis. Cell Death Differ. 2010;17(2):193–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Chen F, Hu SJ. Effect of microRNA-34a in cell cycle, differentiation, and apoptosis: a review. J Biochem Mol Toxicol. 2012;26(2):79–86.CrossRefPubMedGoogle Scholar
  17. 17.
    He C, et al. Functional elucidation of MiR-34 in osteosarcoma cells and primary tumor samples. Biochem Biophys Res Commun. 2009;388(1):35–40.CrossRefPubMedGoogle Scholar
  18. 18.
    Zhou Y, et al. 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.CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    Lee KW, et al. Twist1 is essential in maintaining mesenchymal state and tumor-initiating properties in synovial sarcoma. Cancer Lett. 2014;343(1):62–73.CrossRefPubMedGoogle Scholar
  20. 20.
    Wu J, et al. TWIST interacts with β-catenin signaling on osteosarcoma cell survival against cisplatin. Mol Carcinog. 2014;53(6):440–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Zhou Y, et al. TWIST interacts with endothelin-1/endothelin A receptor signaling in osteosarcoma cell survival against cisplatin. Oncol Lett. 2013;5(3):857–61.PubMedCentralPubMedGoogle Scholar
  22. 22.
    Maire G, et al. Analysis of miRNA-gene expression-genomic profiles reveals complex mechanisms of microRNA deregulation in osteosarcoma. Cancer Genet. 2011;204(3):138–46.CrossRefPubMedGoogle Scholar
  23. 23.
    Wang S, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008;15(2):261–71.CrossRefPubMedCentralPubMedGoogle Scholar
  24. 24.
    Zhang K, et al. 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.PubMedCentralPubMedGoogle Scholar
  25. 25.
    Zhao D, et al. VEGF-mediated suppression of cell proliferation and invasion by miR-410 in osteosarcoma. Mol Cell Biochem. 2015;400(1–2):87–95.CrossRefPubMedGoogle Scholar
  26. 26.
    Kwiecinski M, et al. Expression of platelet-derived growth factor-C and insulin-like growth factor I in hepatic stellate cells is inhibited by miR-29. Lab Invest. 2012;92(7):978–87.CrossRefPubMedGoogle Scholar
  27. 27.
    Czabotar PE, et al. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014;15(1):49–63.CrossRefPubMedGoogle Scholar
  28. 28.
    Trieb K, Sulzbacher I, Kubista B. Bcl-2 correlates with localization but not outcome in human osteosarcoma. Oncol Lett. 2013;6(2):559–61.PubMedCentralPubMedGoogle Scholar
  29. 29.
    Nedelcu T, et al. Livin and Bcl-2 expression in high-grade osteosarcoma. J Cancer Res Clin Oncol. 2008;134(2):237–44.CrossRefPubMedGoogle Scholar
  30. 30.
    Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ. 2010;17(2):215–20.CrossRefPubMedGoogle Scholar
  31. 31.
    Xia L, et al. miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer. 2008;123(2):372–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Zhang H, et al. microRNA-143, down-regulated in osteosarcoma, promotes apoptosis and suppresses tumorigenicity by targeting Bcl-2. Oncol Rep. 2010;24(5):1363–9.PubMedGoogle Scholar
  33. 33.
    Fletcher C, Unni KK, Mertens F. World Health Organization classification of tumors. Lyon: IARC Press; 2002.Google Scholar
  34. 34.
    Rozeman LB, Cleton-Jansen AM, Hogendoorn PC. Pathology of primary malignant bone and cartilage tumours. Int Orthop. 2006;30(6):437–44.CrossRefPubMedCentralPubMedGoogle Scholar
  35. 35.
    Zhu Z, et al. MicroRNA-100 resensitizes resistant chondrosarcoma cells to cisplatin through direct targeting of mTOR. Asian Pac J Cancer Prev. 2014;15(2):917–23.CrossRefPubMedGoogle Scholar
  36. 36.
    Huang J, et al. MicroRNA-100 inhibits osteosarcoma cell proliferation by targeting Cyr61. Tumour Biol. 2014;35(2):1095–100.CrossRefPubMedGoogle Scholar
  37. 37.
    Lauvrak SU, 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.CrossRefPubMedCentralPubMedGoogle Scholar
  38. 38.
    Yoshitaka T, et al. Analysis of microRNAs expressions in chondrosarcoma. J Orthop Res. 2013;31(12):1992–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Petrelli A, et al. By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy. Oncotarget. 2015;6(4):2315–30.PubMedCentralPubMedGoogle Scholar
  40. 40.
    Li Z, et al. MicroRNA-100 regulates pancreatic cancer cells growth and sensitivity to chemotherapy through targeting FGFR3. Tumour Biol. 2014;35(12):11751–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Zhou S, et al. Prognostic value of microRNA-100 in esophageal squamous cell carcinoma. J Surg Res. 2014;192(2):515–20.CrossRefPubMedGoogle Scholar
  42. 42.
    Sarver AL, et al. MicroRNAs at the human 14q32 locus have prognostic significance in osteosarcoma. Orphanet J Rare Dis. 2013;8:7.CrossRefPubMedCentralPubMedGoogle Scholar
  43. 43.
    Wang L, et al. microRNA-377 suppresses the proliferation of human osteosarcoma MG-63 cells by targeting CDK6. Tumour Biol. 2015. doi: 10.1007/s13277-014-3034-2.Google Scholar
  44. 44.
    Namløs HM, et al. Modulation of the osteosarcoma expression phenotype by microRNAs. PLoS ONE. 2012;7(10):e48086.CrossRefPubMedCentralPubMedGoogle Scholar
  45. 45.
    Mak IW, et al. The epigenetic regulation of SOX9 by miR-145 in human chondrosarcoma. J Cell Biochem. 2015;116(1):37–44.CrossRefPubMedGoogle Scholar
  46. 46.
    Lei P, et al. microRNA-145 inhibits osteosarcoma cell proliferation and invasion by targeting ROCK1. Mol Med Rep. 2014;10(1):155–60.PubMedGoogle Scholar
  47. 47.
    Li E, et al. MiR-145 inhibits osteosarcoma cells proliferation and invasion by targeting ROCK1. Tumour Biol. 2014;35(8):7645–50.CrossRefPubMedGoogle Scholar
  48. 48.
    Lochhead PA, et al. Activating ROCK1 somatic mutations in human cancer. Oncogene. 2010;29(17):2591–8.CrossRefPubMedGoogle Scholar
  49. 49.
    Selbach M, et al. Widespread changes in protein synthesis induced by microRNAs. Nature. 2008;455(7209):58–63.CrossRefPubMedGoogle Scholar
  50. 50.
    Zhao G, et al. MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PLoS ONE. 2013;8(1):e53906.CrossRefPubMedCentralPubMedGoogle Scholar
  51. 51.
    Chun-Zhi Z, et al. MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN. BMC Cancer. 2010;10:367.CrossRefPubMedCentralPubMedGoogle Scholar
  52. 52.
    Galardi S, et al. miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1. J Biol Chem. 2007;282(32):23716–24.CrossRefPubMedGoogle Scholar
  53. 53.
    Lim LP, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433(7027):769–73.CrossRefPubMedGoogle Scholar
  54. 54.
    Tang F, et al. MicroRNA expression profiling of single whole embryonic stem cells. Nucleic Acids Res. 2006;34(2):e9.CrossRefPubMedCentralPubMedGoogle Scholar
  55. 55.
    Song B, et al. Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells. Oncogene. 2009;28(46):4065–74.CrossRefPubMedCentralPubMedGoogle Scholar
  56. 56.
    Yuan J, et al. The expression and function of miRNA-451 in osteosarcoma. Med Oncol. 2015;32(1):324.CrossRefPubMedGoogle Scholar
  57. 57.
    Chong Y, et al. MicroRNA-503 acts as a tumor suppressor in osteosarcoma by targeting L1CAM. PLoS ONE. 2014;9(12):e114585.CrossRefPubMedCentralPubMedGoogle Scholar
  58. 58.
    Cai H, et al. Serum miR-195 is a diagnostic and prognostic marker for osteosarcoma. J Surg Res. 2014;194(2):505–10.CrossRefPubMedGoogle Scholar
  59. 59.
    Dylla L, Moore C, Jedlicka P. MicroRNAs in Ewing sarcoma. Front Oncol. 2013;3:65.CrossRefPubMedCentralPubMedGoogle Scholar
  60. 60.
    Karnuth B, 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.CrossRefPubMedCentralPubMedGoogle Scholar
  61. 61.
    Hu H, et al. Changes in microRNA expression in the MG-63 osteosarcoma cell line compared with osteoblasts. Oncol Lett. 2012;4(5):1037–42.PubMedCentralPubMedGoogle Scholar
  62. 62.
    Gao Y, et al. miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via increasing PTEN expression. Biochem Biophys Res Commun. 2014;444(2):230–4.CrossRefPubMedGoogle Scholar
  63. 63.
    Li X, et al. MicroRNA-19b targets Mfn1 to inhibit Mfn1-induced apoptosis in osteosarcoma cells. Neoplasma. 2014;61(3):265–73.CrossRefPubMedGoogle Scholar
  64. 64.
    Wang XH, et al. microRNA-25 promotes osteosarcoma cell proliferation by targeting the cell-cycle inhibitor p27. Mol Med Rep. 2014;10(2):855–9.PubMedGoogle Scholar
  65. 65.
    Montanini L, et al. MicroRNA cloning and sequencing in osteosarcoma cell lines: differential role of miR-93. Cell Oncol (Dordr). 2012;35(1):29–41.CrossRefGoogle Scholar
  66. 66.
    Pei H, et al. MiR-135b promotes proliferation and invasion of osteosarcoma cells via targeting FOXO1. Mol Cell Biochem. 2015;400(1–2):245–52.CrossRefPubMedGoogle Scholar
  67. 67.
    Lulla RR, et al. Identification of differentially expressed MicroRNAs in osteosarcoma. Sarcoma. 2011;2011:732690.CrossRefPubMedCentralPubMedGoogle Scholar
  68. 68.
    Won KY, et al. MicroRNA-199b-5p is involved in the Notch signaling pathway in osteosarcoma. Hum Pathol. 2013;44(8):1648–55.CrossRefPubMedGoogle Scholar
  69. 69.
    Cai H, et al. Prognostic evaluation of microRNA-210 expression in pediatric osteosarcoma. Med Oncol. 2013;30(2):499.CrossRefPubMedGoogle Scholar
  70. 70.
    Wang X, et al. MicroRNA-214 regulates osteosarcoma survival and growth by directly targeting phosphatase and tensin homolog. Mol Med Rep. 2014;10(6):3073–9.PubMedGoogle Scholar
  71. 71.
    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.CrossRefPubMedGoogle Scholar
  72. 72.
    Li H, et al. miR-542-3p overexpression is associated with enhanced osteosarcoma cell proliferation and migration ability by targeting Van Gogh-like 2. Mol Med Rep. 2015;11(2):851–6.PubMedCentralPubMedGoogle Scholar
  73. 73.
    Guo S, 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.CrossRefPubMedGoogle Scholar
  74. 74.
    Wang G, et al. miR-23a suppresses proliferation of osteosarcoma cells by targeting SATB1. Tumour Biol. 2015. doi: 10.1007/s13277-015-3120-0.Google Scholar
  75. 75.
    Zhang W, et al. The microRNA-29 plays a central role in osteosarcoma pathogenesis and progression. Mol Biol (Mosk). 2012;46(4):622–7.Google Scholar
  76. 76.
    Di Fiore R, et al. MicroRNA-29b-1 impairs in vitro cell proliferation, self-renewal and chemoresistance of human osteosarcoma 3AB-OS cancer stem cells. Int J Oncol. 2014;45(5):2013–23.PubMedGoogle Scholar
  77. 77.
    Xu JQ, et al. MicroRNA-32 inhibits osteosarcoma cell proliferation and invasion by targeting Sox9. Tumour Biol. 2014;35(10):9847–53.CrossRefPubMedGoogle Scholar
  78. 78.
    Xu N, et al. MicroRNA-33b suppresses migration and invasion by targeting c-Myc in osteosarcoma cells. PLoS ONE. 2014;9(12):e115300.CrossRefPubMedCentralPubMedGoogle Scholar
  79. 79.
    Lv H, et al. A polymorphism site in the pre-miR-34a coding region reduces miR-34a expression and promotes osteosarcoma cell proliferation and migration. Mol Med Rep. 2014;10(6):2912–6.PubMedCentralPubMedGoogle Scholar
  80. 80.
    Tian Y, Zhang YZ, Chen W. MicroRNA-199a-3p and microRNA-34a regulate apoptosis in human osteosarcoma cells. Biosci Rep. 2014;34(4):479.CrossRefGoogle Scholar
  81. 81.
    Liu Z, et al. The tumor-suppressive microRNA-135b targets c-myc in osteosarcoma. PLoS ONE. 2014;9(7):e102621.CrossRefPubMedCentralPubMedGoogle Scholar
  82. 82.
    Osaki M, et al. MicroRNA-143 regulates human osteosarcoma metastasis by regulating matrix metalloprotease-13 expression. Mol Ther. 2011;19(6):1123–30.CrossRefPubMedCentralPubMedGoogle Scholar
  83. 83.
    Zhao M, 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.PubMedGoogle Scholar
  84. 84.
    Duan Z, et al. MicroRNA-199a-3p is downregulated in human osteosarcoma and regulates cell proliferation and migration. Mol Cancer Ther. 2011;10(8):1337–45.CrossRefPubMedCentralPubMedGoogle Scholar
  85. 85.
    Sun Z, et al. miR-202 suppresses proliferation and induces apoptosis of osteosarcoma cells by downregulating Gli2. Mol Cell Biochem. 2014;397(1–2):277–83.CrossRefPubMedGoogle Scholar
  86. 86.
    Luo XJ, et al. MicroRNA-212 inhibits osteosarcoma cells proliferation and invasion by down-regulation of Sox4. Cell Physiol Biochem. 2014;34(6):2180–8.CrossRefPubMedGoogle Scholar
  87. 87.
    Shen L, et al. MicroRNA-217 regulates WASF3 expression and suppresses tumor growth and metastasis in osteosarcoma. PLoS ONE. 2014;9(10):e109138.CrossRefPubMedCentralPubMedGoogle Scholar
  88. 88.
    Zhang H, et al. Prognostic value of microRNA-223/epithelial cell transforming sequence 2 signaling in patients with osteosarcoma. Hum Pathol. 2014;45(7):1430–6.CrossRefPubMedGoogle Scholar
  89. 89.
    Xu M, et al. miR-382 inhibits tumor growth and enhance chemosensitivity in osteosarcoma. Oncotarget. 2014;5(19):9472–83.PubMedCentralPubMedGoogle Scholar
  90. 90.
    Sun XH, et al. miRNA-646 suppresses osteosarcoma cell metastasis by downregulating fibroblast growth factor 2 (FGF2). Tumour Biol. 2014;36(3):2127–34.CrossRefPubMedGoogle Scholar
  91. 91.
    Xu H, Liu X, Zhao J. Down-regulation of miR-3928 promoted osteosarcoma growth. Cell Physiol Biochem. 2014;33(5):1547–56.CrossRefPubMedGoogle Scholar
  92. 92.
    Poos K, et al. How microRNA and transcription factor co-regulatory networks affect osteosarcoma cell proliferation. PLoS Comput Biol. 2013;9(8):e1003210.CrossRefPubMedCentralPubMedGoogle Scholar
  93. 93.
    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.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Le Chang
    • 1
  • Swati Shrestha
    • 1
  • Greg LaChaud
    • 1
  • Michelle A. Scott
    • 2
  • Aaron W. James
    • 1
    Email author
  1. 1.Department of Pathology and Laboratory Medicine, David Geffen School of MedicineUniversity of California, Los AngelesLos AngelesUSA
  2. 2.Nationwide Children’s HospitalColumbusUSA

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