Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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MicroRNA-100 Resensitizes Resistant Chondrosarcoma Cells to Cisplatin through Direct Targeting of mTOR

  • Zhu, Zhe (Department of Spine Surgery, Qilu Hospital of Shandong University) ;
  • Wang, Cun-Ping (Department of Orthopaedics, Zaozhuang Municipal Hospital) ;
  • Zhang, Yin-Feng (Department of Orthopaedics, Zaozhuang Shizhong People's Hospital) ;
  • Nie, Lin (Department of Spine Surgery, Qilu Hospital of Shandong University)
  • Published : 2014.01.30
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Abstract

Chondrosarcomas are malignant cartilage-forming tumors of bone which exhibit resistance to both chemotherapy and radiation treatment. miRNAs have been well demonstrated to regulate gene expression and play essential roles in a variety of biological processes, including proliferation, differentiation, migration, cell cycling and apoptosis. In this study, we obtained evidence that miR-100 acts as a tumor suppressor in human chondrosarcomas. Interestingly, cisplatin resistant chondrosarcoma cells exhibit decreased expression of miR-100 compared with parental cells. In addition, we identified mTOR as a direct target of miR-100. Overexpression of miR-100 complementary pairs to the 3' untranslated region (UTR) of mTOR, resulted in sensitization of cisplatin resistant cells to cisplatin. Moreover, recovery of the mTOR pathway by overexpression of S6K desensitized the chondrosarcoma cells to cisplatin, suggesting the miR-100-mediated sensitization to cisplatin dependent on inhibition of mTOR. In summary, the present studies highlight miR-100 as a tumor suppressor in chondrosarcoma contributing to anti-chemoresistance. Overexpression of miR-100 might be exploited as a therapeutic strategy along with cisplatin-based combined chemotherapy for the treatment of clinical chondrosarcoma patients.

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References

  1. Ameres SL, Zamore PD (2013). Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol, 14, 475-88. https://doi.org/10.1038/nrm3611
  2. Barr MP, Gray SG, Hoffmann AC, et al (2013). Generation and characterisation of cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature. PLoS One, 8, e54193. https://doi.org/10.1371/journal.pone.0054193
  3. Caron E, Ghosh S, Matsuoka Y, et al (2010). A comprehensive map of the mTOR signaling network. Mol Syst Biol, 21, 453.
  4. Chen P, Zhao X, Ma L (2013). Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in hepatocellular carcinoma. Mol Cell Biochem, 383, 49-58. https://doi.org/10.1007/s11010-013-1753-0
  5. Croce CM (2009). Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet, 10, 704-14. https://doi.org/10.1038/nrg2634
  6. Fiorenza F, Abudu A, Grimer RJ, et al (2002). Risk factors for survival and local control in chondrosarcoma of bone. J Bone Joint Surg Br, 84, 93-9. https://doi.org/10.1302/0301-620X.84B1.11942
  7. Galluzzi L, Senovilla L, Vitale I, et al (2012). Molecular mechanisms of cisplatin resistance. Oncogene, 31, 1869-83. https://doi.org/10.1038/onc.2011.384
  8. Gelderblom H, Hogendoorn PCW, Dijkstra SD, et al (2008). The clinical approach towards chondrosarcoma. Oncologist, 13, 320-9. https://doi.org/10.1634/theoncologist.2007-0237
  9. Germani A, Matrone A, Grossi V, et al (2013). Targeted therapy against chemoresistant colorectal cancers: Inhibition of $p38\alpha$ modulates the effect of cisplatin in vitro and in vivo through the tumor suppressor FoxO3A. Cancer Lett, 344, 110-8.
  10. Henson BJ, Bhattacharjee S, O'Dee DM, Feingold E, Gollin SM (2009). Decreased expression of miR-100 and miR-100 in oral cancer cells contributes to malignancy. Genes Chromosomes Cancer, 48, 569-82. https://doi.org/10.1002/gcc.20666
  11. Juliachs M, Munoz C, Moutinho C, et al (2013). The $PDGFR\beta$-AKT Pathway Contributes To CDDP-Acquired Resistance In Testicular Germ Cell Tumors. Clin Cancer Res, [Epub ahead of print]
  12. Laplante M, Sabatini DM (2012). mTOR signaling in growth control and disease. Cell, 13, 274-93.
  13. Li H, Zhang X, Song X (2012). PDCD5 promotes cisplatininduced apoptosis of glioma cells via activating mitochondrial apoptotic pathway. Cancer Biol Ther, 13, 822-30. https://doi.org/10.4161/cbt.20565
  14. Lin C, McGough R, Aswad B, Block JA, Terek R (2004). Hypoxia induces HIF-1alpha and VEGF expression in chondrosarcoma cells and chondrocytes. J Orthop Res, 22, 1175-81. https://doi.org/10.1016/j.orthres.2004.03.002
  15. Liu J, Lu KH, Liu ZL, et al (2012). MicroRNA-100 is a potential molecular marker of non-small cell lung cancer and functions as a tumor suppressor by targeting polo-like kinase 1. BMC Cancer, 14, 519.
  16. Ma J, Dong C, Ji C, et al (2010). MicroRNA and drug resistance. Cancer Gene Ther. 17, 523-31. https://doi.org/10.1038/cgt.2010.18
  17. Mabuchi S, Altomare DA, Cheung M, et al (2007). RAD001 inhibits human ovarian cancer cell proliferation, enhances cisplatin-induced apoptosis, and prolongs survival in an ovarian cancer model. Clin Cancer Res, 13, 4261-70. https://doi.org/10.1158/1078-0432.CCR-06-2770
  18. Mir R, Stanzani E, Martinez-Soler F, Villanueva A, et al (2013). YM155 sensitizes ovarian cancer cells to cisplatin inducing apoptosis and tumor regression. Gynecol Oncol, 132, 211-20.
  19. Nagaraja AK, Creighton CJ, Yu Z, et al (2010). A link between mir-100 and FRAP1/mTOR in clear cell ovarian cancer. Mol Endocrinol, 24, 447-63. https://doi.org/10.1210/me.2009-0295
  20. Negoro K, Yamano Y, Fushimi K, et al (2007). Establishment and characterization of a cisplatin-resistant cell line, KB-R, derived from oral carcinoma cell line, KB. Int J Oncol, 30, 1325-32.
  21. Onishi AC, Hincker AM, Lee FY (2011). Surmounting chemotherapy and radioresistance in chondrosarcoma: molecular mechanisms and therapeutic targets. Sarcoma, 2011, 381564.
  22. Parsch D, Brassat U, Brummendorf TH, Fellenberg J (2008). Consequences of telomerase inhibition by BIBR1532 on proliferation and chemosensitivity of chondrosarcoma cell lines. Cancer Invest, 26, 590-6. https://doi.org/10.1080/07357900802072905
  23. Pendleton KP, Grandis JR (2013). Cisplatin-Based Chemotherapy Options for Recurrent and/or Metastatic Squamous Cell Cancer of the Head and Neck. Clin Med Insights Ther, 2013, S10409
  24. Schrage YM, Lam S, Jochemsen AG, et al (2009). Central chondrosarcoma progression is associated with pRb pathway alterations: CDK4 down-regulation and p16 overexpression inhibit cell growth in vitro. J Cell Mol Med, 13, 2843-52. https://doi.org/10.1111/j.1582-4934.2008.00406.x
  25. Shin DH, Choi YJ, Park JW (2013). SIRT1 and AMPK mediate hypoxia-induced resistance of non-small cell lung cancers to cisplatin and doxorubicin. Cancer Res, [Epub ahead of print]
  26. Steelman LS, Navolanic P, Chappell WH, et al (2011). Involvement of Akt and mTOR in chemotherapeutic- and hormonal-based drug resistance and response to radiation in breast cancer cells. Cell Cycle, 10, 3003-15. https://doi.org/10.4161/cc.10.17.17119
  27. Sternberg CN, Skoneczna IA, Castellano D, et al (2013). Larotaxel with Cisplatin in the First-Line Treatment of Locally Advanced/Metastatic Urothelial Tract or Bladder Cancer: A Randomized, Active-Controlled, Phase III Trial (CILAB). Oncology, 85, 208-15. https://doi.org/10.1159/000354085
  28. Van Oosterwijk JG, Anninga JK, Gelderblom H, Cleton-Jansen AM, Bovee JV (2013). Update on targets and novel treatment options for high-grade osteosarcoma and chondrosarcoma. Hematol Oncol Clin North Am, 27, 1021-48. https://doi.org/10.1016/j.hoc.2013.07.012
  29. Wang J, Zhou JY, Zhang L, Wu GS (2009). Involvement of MKP-1 and Bcl-2 in acquired cisplatin resistance in ovarian cancer cells. Cell Cycle, 8, 3191-8. https://doi.org/10.4161/cc.8.19.9751
  30. Xu C, Zeng Q, Xu W, et al (2013). miRNA-100 inhibits human bladder urothelial carcinogenesis by directly targeting mTOR. Mol Cancer Ther, 12, 207-19. https://doi.org/10.1158/1535-7163.MCT-12-0273
  31. Yardley DA (2013). Combining mTOR Inhibitors with Chemotherapy and Other Targeted Therapies in Advanced Breast Cancer: Rationale, Clinical Experience, and Future Directions. Breast Cancer, 7, 7-22.
  32. Yoshitaka T, Kawai A, Miyaki S, et al (2013). Analysis of microRNAs expressions in chondrosarcoma. J Orthop Res, 31, 1992-8. https://doi.org/10.1002/jor.22457
  33. Zhang YX, van Oosterwijk JG, Sicinska E, et al (2013). Functional profiling of receptor tyrosine kinases and downstream signaling in human chondrosarcomas identifies pathways for rational targeted therapy. Clin Cancer Res, 19, 3796-807. https://doi.org/10.1158/1078-0432.CCR-12-3647
  34. Zheng T, Wang J, Chen X, Liu L (2010). Role of microRNA in anticancer drug resistance. Int J Cancer, 126, 2-10. https://doi.org/10.1002/ijc.24782

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