Skip to main content

Advertisement

Log in

Histone demethylase JMJD2B and JMJD2C induce fibroblast growth factor 2: mediated tumorigenesis of osteosarcoma

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

JMJD2B and JMJD2C, histone demethylases, play crucial roles in cancer development and are up-regulated in many cancers. However, the actions of JMJD2B and JMJD2C in osteosarcoma remain unknown. The levels of JMJD2B or JMJD2C were evaluated in osteosarcoma cells and tissues via quantitative real-time PCR and Western Blot. JMJD2B and JMJD2C were up-regulated in osteosarcoma tissues when compared to paired adjacent non-tumor tissues. A higher level of JMJD2B or JMJD2C was related with metastasis of osteosarcoma cells. Fibroblast growth factor 2 (FGF2) is an important factor to maintain immaturity of cells and contributes to osteosarcoma aggressiveness. Elevated levels of FGF2 promoted the proliferation, migration, and invasion of osteosarcoma cell, while FGF2 was up-regulated by JMJD2B or JMJD2C. GST pull-down assay showed that JMJD2B or JMJD2C interacted with FGF2. Thus, JMJD2B and JMJD2C play an important role in the pathology of osteosarcoma via the up-regulation of FGF2. JMJD2B and JMJD2C should be developed potential targets for the therapy of osteosarcoma patients.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Lee JS, DuBois SG, Boscardin WJ, et al. Secondary malignant neoplasms among children, adolescents, and young adults with osteosarcoma. Cancer. 2014;120(24):3987–93.

    Article  PubMed  Google Scholar 

  2. Pradhan A., Reddy KI, Grimer RJ, et al. Osteosarcomas in the upper distal extremities: are their oncological outcomes similar to other sites? Eur J Surg Oncol. 2014.

  3. DeAngelis AF, Spinou C, Tsui A, et al. Outcomes of patients with maxillofacial osteosarcoma: a review of 15 cases. J Oral Maxillofac Surg. 2012;70(3):734–9.

    Article  PubMed  Google Scholar 

  4. Lu Y, Chang Q, Zhang Y, et al. Lung cancer-associated JmjC domain protein mdig suppresses formation of tri-methyl lysine 9 of histone H3. Cell Cycle. 2009;8(13):2101–9.

    Article  CAS  PubMed  Google Scholar 

  5. Shin S, Janknecht R. Activation of androgen receptor by histone demethylases JMJD2A and JMJD2D. Biochem Biophys Res Commun. 2007;359(3):742–6.

    Article  CAS  PubMed  Google Scholar 

  6. Khoury-Haddad H, Guttmann-Raviv N, Ipenberg I, et al. PARP1-dependent recruitment of KDM4D histone demethylase to DNA damage sites promotes double-strand break repair. Proc Natl Acad Sci USA. 2014;111(7):E728–37.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Kycia I, Kudithipudi S, Tamas R, et al. The tudor domain of the PHD finger protein 1 is a dual reader of lysine trimethylation at lysine 36 of histone H3 and lysine 27 of histone variant H3t. J Mol Biol. 2014;426(8):1651–60.

    Article  CAS  PubMed  Google Scholar 

  8. Whetstine JR, Nottke A, Lan F, et al. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell. 2006;125(3):467–81.

    Article  CAS  PubMed  Google Scholar 

  9. Trojer P, Zhang J, Yonezawa M, et al. Dynamic histone H1 isotype 4 methylation and demethylation by histone lysine methyltransferase G9a/KMT1C and the Jumonji domain-containing JMJD2/KDM4 proteins. J Biol Chem. 2009;284(13):8395–405.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Berry WL, Janknecht R. KDM4/JMJD2 histone demethylases: epigenetic regulators in cancer cells. Cancer Res. 2013;73(10):2936–42.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Kim TD, Fuchs JR, Schwartz E, et al. Pro-growth role of the JMJD2C histone demethylase in HCT-116 colon cancer cells and identification of curcuminoids as JMJD2 inhibitors. Am J Transl Res. 2014;6(3):236–47.

    PubMed Central  PubMed  Google Scholar 

  12. Li LL, Xue AM, Li BX, et al. JMJD2A contributes to breast cancer progression through transcriptional repression of the tumor suppressor ARHI. Breast Cancer Res. 2014;16(3):R56.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Kim TD, Shin S, Berry WL, et al. The JMJD2A demethylase regulates apoptosis and proliferation in colon cancer cells. J Cell Biochem. 2012;113(4):1368–76.

    Article  CAS  PubMed  Google Scholar 

  14. Hu CE, Liu YC, Zhang HD, et al. JMJD2A predicts prognosis and regulates cell growth in human gastric cancer. Biochem Biophys Res Commun. 2014;449(1):1–7.

    Article  CAS  PubMed  Google Scholar 

  15. Kauffman EC, Robinson BD, Downes MJ, et al. Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer. Mol Carcinog. 2011;50(12):931–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Mallette FA, Richard S. JMJD2A promotes cellular transformation by blocking cellular senescence through transcriptional repression of the tumor suppressor CHD5. Cell Rep. 2012;2(5):1233–43.

    Article  CAS  PubMed  Google Scholar 

  17. Sun BB, Fu LN, Wang YQ, et al. Silencing of JMJD2B induces cell apoptosis via mitochondria-mediated and death receptor-mediated pathway activation in colorectal cancer. J Dig Dis. 2014;15(9):491–500.

    Article  CAS  PubMed  Google Scholar 

  18. Zhao L, Li W, Zang W, et al. JMJD2B promotes epithelial-mesenchymal transition by cooperating with beta-catenin and enhances gastric cancer metastasis. Clin Cancer Res. 2013;19(23):6419–29.

    Article  CAS  PubMed  Google Scholar 

  19. Kawazu M, Saso K, Tong KI, et al. Histone demethylase JMJD2B functions as a co-factor of estrogen receptor in breast cancer proliferation and mammary gland development. PLoS ONE. 2011;6(3):e17830.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Hong Q, Yu S, Yang Y, et al. A polymorphism in JMJD2C alters the cleavage by caspase-3 and the prognosis of human breast cancer. Oncotarget. 2014;5(13):4779–87.

    PubMed Central  PubMed  Google Scholar 

  21. Kim TD, Oh S, Shin S, et al. Regulation of tumor suppressor p53 and HCT116 cell physiology by histone demethylase JMJD2D/KDM4D. PLoS ONE. 2012;7(4):e34618.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Ren T, Qing Y, Dai N, et al. Apurinic/apyrimidinic endonuclease 1 induced upregulation of fibroblast growth factor 2 and its receptor 3 induces angiogenesis in human osteosarcoma cells. Cancer Sci. 2014;105(2):186–94.

    Article  CAS  PubMed  Google Scholar 

  23. Luo L, King NP, Yeo JC, et al. Single-step protease cleavage elution for identification of protein-protein interactions from GST pull-down and mass spectrometry. Proteomics. 2014;14(1):19–23.

    Article  CAS  PubMed  Google Scholar 

  24. Kweldam CF, Wildhagen MF, Steyerberg EW, et al. Cribriform growth is highly predictive for postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer. Mod Pathol. 2014.

  25. Tee AE, Ling D, Nelson C, et al. The histone demethylase JMJD1A induces cell migration and invasion by up-regulating the expression of the long noncoding RNA MALAT1. Oncotarget. 2014;5(7):1793–804.

    PubMed Central  PubMed  Google Scholar 

  26. Nakayama F, Umeda S, Yasuda T, et al. Cellular internalization of fibroblast growth factor-12 exerts radioprotective effects on intestinal radiation damage independently of FGFR signaling. Int J Radiat Oncol Biol Phys. 2014;88(2):377–84.

    Article  CAS  PubMed  Google Scholar 

  27. Feng S, Zhou L, Nice EC, et al. Fibroblast growth factor receptors: multifactorial-contributors to tumor initiation and progression. Histol Histopathol. 2015;30(1):13–31.

    CAS  PubMed  Google Scholar 

  28. Donnem T, Al-Shibli K, Al-Saad S, et al. Prognostic impact of fibroblast growth factor 2 in non-small cell lung cancer: coexpression with VEGFR-3 and PDGF-B predicts poor survival. J Thorac Oncol. 2009;4(5):578–85.

    Article  PubMed  Google Scholar 

  29. Hoefer J, Kern J, Ofer P, et al. SOCS2 correlates with malignancy and exerts growth-promoting effects in prostate cancer. Endocr Relat Cancer. 2014;21(2):175–87.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Tsunoda S, Nakamura T, Sakurai H, et al. Fibroblast growth factor-2-induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A-dependent neovascularization. Cancer Sci. 2007;98(4):541–8.

    Article  CAS  PubMed  Google Scholar 

  31. Wang L, Park H, Chhim S, et al. A novel monoclonal antibody to fibroblast growth factor 2 effectively inhibits growth of hepatocellular carcinoma xenografts. Mol Cancer Ther. 2012;11(4):864–72.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors had no conflicts of interest to declare in relation to this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiaojiang Li.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, X., Dong, S. Histone demethylase JMJD2B and JMJD2C induce fibroblast growth factor 2: mediated tumorigenesis of osteosarcoma. Med Oncol 32, 53 (2015). https://doi.org/10.1007/s12032-015-0503-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-015-0503-4

Keywords

Navigation