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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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Volume 396, Issue 8

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SIRT2 suppresses non-small cell lung cancer growth by targeting JMJD2A

Weihua Xu
  • Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China
  • Other articles by this author:
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/ Kanqiu Jiang
  • Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China
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/ Mingjing Shen
  • Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China
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/ Yongyue Qian
  • Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China
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/ Yong Peng
  • Corresponding author
  • Department of Cardiothoracic Surgery, Suzhou Municipal Hospital, 26 Daoqian Street, Suzhou 215002, Jiangsu, China
  • Email
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Published Online: 2015-03-14 | DOI: https://doi.org/10.1515/hsz-2014-0284

Abstract

Lung cancer has been the most prolific cancer in China – as in the rest of the world – with a high death rate and low 5-year survival rate. Previous evidence showed that JMJD2A is over-expressed in human non-small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues, and that high level of JMJD2A predicts poor overall and disease-free survival. However, the mechanism by which JMJD2A is regulated in human NSCLC is not fully understood. In the present study, we identified that the SIRT2 as an anti-oncogenic protein in NSCLC was down-regulated. JMJD2A as a target of SIRT2 was negatively correlated with SIRT2 level in NSCLC. SIRT2 bound to the promoter region of JMJD2A and negatively regulated JMJD2A expression. In addition, we found that SIRT2 inhibited NSCLC cells proliferation, colony formation and tumor growth in vitro and in vivo in a JMJD2A-dependent manner. In summary, our findings implicate that SIRT2 suppresses non-small cell lung cancer growth through targeting JMJD2A and SIRT2 activator may serve as candidate drug for NSCLC therapy.

This article offers supplementary material which is provided at the end of the article.

Keywords: human non-small cell lung cancer; JMJD2A; SIRT2

References

  • Arora, A. and Dey, C.S. (2014). SIRT2 negatively regulates insulin resistance in C2C12 skeletal muscle cells. Biochim. Biophys. Acta Mol. Basis Dis. 1842, 1372–1378.Google Scholar

  • Beirowski, B., Gustin, J., Armour, S.M., Yamamoto, H., Viader, A., North, B.J., Michán, S., Baloh, R.H., Golden, J.P., and Schmidt, R.E. (2011). Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling. Proc. Natl. Acad. Sci. USA 108, E952–E961.Web of ScienceGoogle Scholar

  • Berry, W.L., Shin, S., Lightfoot, S.A., and Janknecht, R. (2012). Oncogenic features of the JMJD2A histone demethylase in breast cancer. Int. J. Oncol. 41, 1701–1706.Web of ScienceGoogle Scholar

  • Carney, D.N. and Hansen, H.H. (2000). Non-small-cell lung cancer – stalemate or progress? N. Engl. J. Med. 343, 1261–1262.Google Scholar

  • Cheon, M.G., Kim, W., Choi, M., and Kim, J.E. (2015). AK-1, a specific SIRT2 inhibitor, induces cell cycle arrest by downregulating Snail in HCT116 human colon carcinoma cells. Cancer Lett. 356, 637–645.Google Scholar

  • Das, A., Chai, J.C., Jung, K.H., Das, N.D., Kang, S.C., Lee, Y.S., Seo, H., and Chai, Y.G. (2014). JMJD2A attenuation affects cell cycle and tumourigenic inflammatory gene regulation in lipopolysaccharide stimulated neuroectodermal stem cells. Exp. Cell Res. 328, 361–378.Web of ScienceGoogle Scholar

  • Fodor, B.D., Kubicek, S., Yonezawa, M., O’Sullivan, R.J., Sengupta, R., Perez-Burgos, L., Opravil, S., Mechtler, K., Schotta, G., and Jenuwein, T. (2006). JMJD2B antagonizes H3K9 trimethylation at pericentric heterochromatin in mammalian cells. Genes Dev. 20, 1557–1562.Google Scholar

  • Gal, J., Bang, Y., and Choi, H.J. (2012). SIRT2 interferes with autophagy-mediated degradation of protein aggregates in neuronal cells under proteasome inhibition. Neurochem. Int. 61, 992–1000.Web of ScienceGoogle Scholar

  • Han, W., Xin, Z., Zhao, Z., Bao, W., Lin, X., Yin, B., Zhao, J., Yuan, J., Qiang, B., and Peng, X. (2013). RNA-binding protein PCBP2 modulates glioma growth by regulating FHL3. J. Clin. Invest. 123, 2103–2118.Google Scholar

  • Hiratsuka, M., Inoue, T., Toda, T., Kimura, N., Shirayoshi, Y., Kamitani, H., Watanabe, T., Ohama, E., Tahimic, C.G., and Kurimasa, A. (2003). Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene. Biochem. Biophys. Res. Commun. 309, 558–566.Google Scholar

  • Hu, C.E., Liu, Y.C., Zhang, H.D., and Huang, G.J. (2014). JMJD2A predicts prognosis and regulates cell growth in human gastric cancer. Biochem. Biophys. Res. Commun. 449, 1–7.Web of ScienceGoogle Scholar

  • Jemal, A., Bray, F., Center, M.M., Ferlay, J., Ward, E., and Forman, D. (2011). Global cancer statistics. CA Cancer J. Clin. 61, 69–90.Google Scholar

  • Kauffman, E.C., Robinson, B.D., Downes, M.J., Powell, L.G., Lee, M.M., Scherr, D.S., Gudas, L.J., and Mongan, N.P. (2011). Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer. Mol. Carcinog. 50, 931–944.Web of ScienceGoogle Scholar

  • Kim, H.S., Vassilopoulos, A., Wang, R.H., Lahusen, T., Xiao, Z., Xu, X., Li, C., Veenstra, T.D., Li, B., and Yu, H. (2011). SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell 20, 487–499.Web of ScienceGoogle Scholar

  • Kogure, M., Takawa, M., Cho, H.S., Toyokawa, G., Hayashi, K., Tsunoda, T., Kobayashi, T., Daigo, Y., Sugiyama, M., and Atomi, Y. (2013). Deregulation of the histone demethylase JMJD2A is involved in human carcinogenesis through regulation of the G1S transition. Cancer Lett. 336, 76–84.Web of ScienceGoogle Scholar

  • Kooistra, S.M. and Helin, K. (2012). Molecular mechanisms and potential functions of histone demethylases. Nat. Rev. Mol. Cell Biol. 13, 297–311.Web of ScienceGoogle Scholar

  • Kouzarides, T. (2007). Chromatin modifications and their function. Cell 128, 693–705.Google Scholar

  • Kubota, S., Fukumoto, Y., Aoyama, K., Ishibashi, K., Yuki, R., Morinaga, T., Honda, T., Yamaguchi, N., Kuga, T., Tomonaga, T., et al. (2013). Phosphorylation of KRAB-associated protein 1 (KAP1) at Tyr-449, Tyr-458, and Tyr-517 by nuclear tyrosine kinases inhibits the association of KAP1 and heterochromatin protein 1α (HP1α) with heterochromatin. J. Biol. Chem. 288, 17871–17883.Web of ScienceGoogle Scholar

  • Kwon, D.W. and Ahn, S.H. (2011). Role of yeast JmjC-domain containing histone demethylases in actively transcribed regions. Biochem. Biophys. Res. Commun. 410, 614–619.Web of ScienceGoogle Scholar

  • Langevin, S.M., Kratzke, R.A., and Kelsey, K.T. (2015). Epigenetics of lung cancer. Transl. Res. 165, 74–90.Web of ScienceGoogle Scholar

  • Lee, A.S., Jung, Y.J., Kim, D., Nguyen-Thanh, T., Kang, K.P., Lee, S., Park, S.K., and Kim, W. (2014). SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages. Biochem. Biophys. Res. Commun. 450, 1363–1369.Web of ScienceGoogle Scholar

  • Li, Y., Dai, D., Lu, Q., Fei, M., Li, M., and Wu, X. (2013a). Sirt2 suppresses glioma cell growth through targeting NF-κB–miR-21 axis. Biochem. Biophys. Res. Commun. 441, 661–667.Google Scholar

  • Li, Z., Xie, Q.R., Chen, Z., Lu, S., and Xia, W. (2013b). Regulation of SIRT2 levels for human non-small cell lung cancer therapy. Lung Cancer 82, 9–15.Web of ScienceGoogle Scholar

  • Mallette, F.A. and Richard, S. (2012). JMJD2A promotes cellular transformation by blocking cellular senescence through transcriptional repression of the tumor suppressor CHD5. Cell Rep. 2, 1233–1243.Web of ScienceGoogle Scholar

  • Mostafa, A.A. and Morris, D.G. (2014). Immunotherapy for lung cancer: has it finally arrived? Front. Oncol. 4, 288.Google Scholar

  • Narayan, N., Lee, I.H., Borenstein, R., Sun, J., Wong, R., Tong, G., Fergusson, M.M., Liu, J., Rovira, I.I., and Cheng, H.L. (2012). The NAD-dependent deacetylase SIRT2 is required for programmed necrosis. Nature 492, 199–204.Web of ScienceGoogle Scholar

  • North, B.J. and Verdin, E. (2007). Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis. PLoS One 2, e784.Google Scholar

  • Peck, B., Chen, C.Y., Ho, K.K., Di Fruscia, P., Myatt, S.S., Coombes, R.C., Fuchter, M.J., Hsiao, C.D., and Lam, E.W. (2010). SIRT inhibitors induce cell death and p53 acetylation through targeting both SIRT1 and SIRT2. Mol. Cancer Ther. 9, 844–855.Google Scholar

  • Risch, A. and Plass, C. (2008). Lung cancer epigenetics and genetics, Int. J. Cancer 123, 1–7.Google Scholar

  • Shin, S. and Janknecht, R. (2007). Activation of androgen receptor by histone demethylases JMJD2A and JMJD2D. Biochem. Biophys. Res. Commun. 359, 742–746.Web of ScienceGoogle Scholar

  • Suematsu, T., Li, Y., Kojima, H., Nakajima, K., Oshimura, M., and Inoue T. (2014). Deacetylation of the mitotic checkpoint protein BubR1 at lysine 250 by SIRT2 and subsequent effects on BubR1 degradation during the prometaphase/anaphase transition. Biochem. Biophys. Res. Commun. 453, 588–594.Web of ScienceGoogle Scholar

  • Wang, J., Zhang, M., Zhang, Y., Kou, Z., Han, Z., Chen, D.Y., Sun, Q.Y., and Gao, S. (2010). The histone demethylase JMJD2C is stage-specifically expressed in preimplantation mouse embryos and is required for embryonic development. Biol. Reprod. 82, 105–111.Web of ScienceGoogle Scholar

  • Young, L.C. and Hendzel, M.J. (2012). The oncogenic potential of Jumonji D2 (JMJD2/KDM4) histone demethylase overexpression. Biochem. Cell Biol. 91, 369–377.Web of ScienceGoogle Scholar

  • Zhao, Y., Wang, S., Aunan, K., Martin Seip, H., and Hao, J. (2006). Air pollution and lung cancer risks in China – a meta-analysis. Sci. Total. Environ. 366, 500–513.Google Scholar

About the article

Corresponding author: Yong Peng, Department of Cardiothoracic Surgery, Suzhou Municipal Hospital, 26 Daoqian Street, Suzhou 215002, Jiangsu, China, e-mail:

aThese authors contributed equally to this work.


Received: 2014-12-01

Accepted: 2015-02-12

Published Online: 2015-03-14

Published in Print: 2015-08-01


Citation Information: Biological Chemistry, Volume 396, Issue 8, Pages 929–936, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2014-0284.

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