Advertisement

Biochemistry (Moscow)

, Volume 77, Issue 8, pp 934–940 | Cite as

HDAC1/DNMT3A-containing complex is associated with suppression of Oct4 in cervical cancer cells

  • Dongbo Liu
  • Peng Zhou
  • Li Zhang
  • Wei Gong
  • Gang Huang
  • Yingru ZhengEmail author
  • Fengtian HeEmail author
Article

Abstract

Octamer-binding transcription factor 4 (Oct4), an important embryonic transcriptional factor, is highly expressed in several tumors and is considered as a hallmark of cancer stem cells. Knowledge about the expression and regulatory mechanisms of Oct4 can contribute to the treatment of cancers. As for cervical cancer, however, details remain obscure about Oct4 expression and its regulatory mechanism. In this study, we found that the level of Oct4 in human papillomavirus 16 (HPV16)-positive cervical cancer cells (CaSki cells) was higher than that in HPV-negative cervical cancer cells (C-33A cells), whereas both the level of histone deacetylase 1 (HDAC1) and DNA methyltransferase 3A (DNMT3A) were lower in CaSki cells than those in C-33A cells. Treatment with valproic acid, an HDAC inhibitor, could significantly increase the expression of Oct4 in C-33A cells, but only slightly increased Oct4 in CaSki cells. Co-immunoprecipitation assays showed that HDAC1 and DNMT3A existed in a common complex. The co-immunoprecipitated DNMT3A or HDAC1 was dose-dependently decreased with valproic acid treatment. These results indicated that HDAC1/DNMT3A-containing complex is associated with the suppression of Oct4 in cervical cancer cells, and the activity of HDAC1 is required in the repression of Oct4.

Key words

Oct4 cervical cancer HDAC1 DNMT3A HPV16 

Abbreviations

CSC

cancer stem cells

DAPI

4,6-diamidino-2-phenylindole

DMEM

Dulbecco’s modified Eagle’s media

DNMT

DNA methyltransferase

GAPDH

glyceraldehyde-3-phosphate dehydrogenase

HDAC

histone deacetylase

HEPES

4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid

HPV

human papillomavirus

IP

immunoprecipitation

Oct4

Octamer-binding transcription factor 4

qPCR

quantitative real time polymerase chain reaction

RT-PCR

semiquantitative reverse transcriptional polymerase chain reaction

VPA

valproic acid

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kashyap, V., Rezende, N. C., Scotland, K. B., Shaffer, S. M., Persson, J. L., Gudas, L. J., and Mongan, N. P. (2009) Stem Cells Dev., 18, 1093–1108.PubMedCrossRefGoogle Scholar
  2. 2.
    Tai, M. H., Chang, C. C., Kiupel, M., Webster, J. D., Olson, L. K., and Trosko, J. E. (2005) Carcinogenesis, 26, 495–502.PubMedCrossRefGoogle Scholar
  3. 3.
    Friedman, S., Lu, M., Schultz, A., Thomas, D., and Lin, R. Y. (2009) PLoS One, 4, e5395.PubMedCrossRefGoogle Scholar
  4. 4.
    Du, Z., Jia, D., Liu, S., Wang, F., Li, G., Zhang, Y., Cao, X., Ling, E. A., and Hao, A. (2009) Glia, 57, 724–733.PubMedCrossRefGoogle Scholar
  5. 5.
    Zhu, Z., Wen, J., Zheng, X., Wang, D., Wang, Q., and Fan, C. (2009) J. Huazhong Univ. Sci. Technol. Med. Sci., 29, 73–76.PubMedCrossRefGoogle Scholar
  6. 6.
    Hu, T., Liu, S., Breiter, D. R., Wang, F., Tang, Y., and Sun, S. (2008) Cancer Res., 68, 6533–6540.PubMedCrossRefGoogle Scholar
  7. 7.
    Woodman, C. B., Collins, S. I., and Young, L. S. (2007) Nat. Rev. Cancer, 7, 11–22.PubMedCrossRefGoogle Scholar
  8. 8.
    Boulet, G., Horvath, C., Vanden, B. D., Sahebali, S., and Bogers, J. (2007) Int. J. Biochem. Cell Biol., 39, 2006–2011.PubMedCrossRefGoogle Scholar
  9. 9.
    Hamid, N. A., Brown, C., and Gaston, K. (2009) Cell Mol. Life Sci., 66, 1700–1717.PubMedCrossRefGoogle Scholar
  10. 10.
    Thomas, M., Narayan, N., Pim, D., Tomaic, V., Massimi, P., Nagasaka, K., Kranjec, C., Gammoh, N., and Banks, L. (2008) Oncogene, 27, 7018–7030.PubMedCrossRefGoogle Scholar
  11. 11.
    Munger, K., Basile, J. R., Duensing, S., Eichten, A., Gonzalez, S. L., Grace, M., and Zacny, V. L. (2001) Oncogene, 20, 7888–7898.PubMedCrossRefGoogle Scholar
  12. 12.
    Feng, D., Peng, C., Li, C., Zhou, Y., Li, M., Ling, B., Wei, H., and Tian, Z. (2009) Oncol. Rep., 22, 1129–1134.PubMedGoogle Scholar
  13. 13.
    Gu, P., Goodwin, B., Chung, A. C., Xu, X., Wheeler, D. A., Price, R. R., Galardi, C., Peng, L., Latour, A. M., Koller, B. H., Gossen, J., Kliewer, S. A., and Cooney, A. J. (2005) Mol. Cell Biol., 25, 3492–3505.PubMedCrossRefGoogle Scholar
  14. 14.
    Yang, H. M., Do, H. J., Kim, D. K., Park, J. K., Chang, W. K., Chung, H. M., Choi, S. Y., and Kim, J. H. (2007) J. Cell Biochem., 101, 1198–1209.PubMedCrossRefGoogle Scholar
  15. 15.
    Xu, N., Papagiannakopoulos, T., Pan, G., Thomson, J. A., and Kosik, K. S. (2009) Cell, 137, 647–658.PubMedCrossRefGoogle Scholar
  16. 16.
    Gunaratne, P. H. (2009) Curr. Stem Cell Res. Ther., 4, 168–177.PubMedCrossRefGoogle Scholar
  17. 17.
    Wei, F., Scholer, H. R., and Atchison, M. L. (2007) J. Biol. Chem., 282, 21551–21560.PubMedCrossRefGoogle Scholar
  18. 18.
    Miranda, T. B., and Jones, P. A. (2007) J. Cell Physiol., 213, 384–390.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang, H. J., Siu, M. K., Wong, E. S., Wong, K. Y., Li, A. S., Chan, K. Y., Ngan, H. Y., and Cheung, A. N. (2008) Placenta, 29, 549–554.PubMedCrossRefGoogle Scholar
  20. 20.
    Liang, J., Wan, M., Zhang, Y., Gu, P., Xin, H., Jung, S. Y., Qin, J., Wong, J., Cooney, A. J., Liu, D., and Songyang, Z. (2008) Nat. Cell Biol., 10, 731–739.PubMedCrossRefGoogle Scholar
  21. 21.
    Wernig, M., Meissner, A., Foreman, R., Brambrink, T., Ku, M., Hochedlinger, K., Bernstein, B. E., and Jaenisch, R. (2007) Nature, 448, 318–324.PubMedCrossRefGoogle Scholar
  22. 22.
    Feldman, N., Gerson, A., Fang, J., Li, E., Zhang, Y., Shinkai, Y., Cedar, H., and Bergman, Y. (2006) Nat. Cell Biol., 8, 188–194.PubMedCrossRefGoogle Scholar
  23. 23.
    Liu, D., Zhou, P., Zhang, L., Wu, G., Zheng, Y., and He, F. (2011) Tumour Biol., 32, 941–950.PubMedCrossRefGoogle Scholar
  24. 24.
    Liedtke, S., Enczmann, J., Waclawczyk, S., Wernet, P., and Kogler, G. (2007) Cell Stem Cell, 1, 364–366.PubMedCrossRefGoogle Scholar
  25. 25.
    Zhao, S., Yuan, Q., Hao, H., Guo, Y., Liu, S., Zhang, Y., Wang, J., Liu, H., Wang, F., Liu, K., Ling, E. A., and Hao, A. (2011) J. Pathol., 223, 672–682.PubMedCrossRefGoogle Scholar
  26. 26.
    Suo, G., Han, J., Wang, X., Zhang, J., Zhao, Y., and Dai, J. (2005) Biochem. Biophys. Res. Commun., 337, 1047–1051.PubMedCrossRefGoogle Scholar
  27. 27.
    Cauffman, G., Liebaers, I., van Steirteghem, A., and van de Velde, H. (2006) Stem Cells, 24, 2685–2691.PubMedCrossRefGoogle Scholar
  28. 28.
    Lee, J., Kim, H. K., Rho, J. Y., Han, Y. M., and Kim, J. (2006) J. Biol. Chem., 281, 33554–33565.PubMedCrossRefGoogle Scholar
  29. 29.
    Rajasingh, J., Thangavel, J., Siddiqui, M. R., Gomes, I., Gao, X. P., Kishore, R., and Malik, A. B. (2011) PLoS One, 6, e22550.PubMedCrossRefGoogle Scholar
  30. 30.
    Kang, H., and Roh, S. (2011) J. Vet. Med. Sci., 73, 623–631.PubMedCrossRefGoogle Scholar
  31. 31.
    Fuks, F., Burgers, W. A., Godin, N., Kasai, M., and Kouzarides (2001) EMBO J., 20, 2536–2544.PubMedCrossRefGoogle Scholar
  32. 32.
    Denis, H., Deplus, R., Putmans, P., Yamada, M., Metivier, R., and Fuks, F. (2009) Mol. Cell Biol., 29, 4982–4993.PubMedCrossRefGoogle Scholar
  33. 33.
    Bodily, J. M., Mehta, K. P., and Laimins, L. A. (2011) Cancer Res., 71, 1187–1195.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2012

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyThird Military Medical UniversityChongqingChina
  2. 2.Depeartment 1 of State Key Laboratory of Trauma, Burns, and Combined InjuryDaping Hospital and Institute of Surgery ResearchChongqingChina
  3. 3.Department of Obstetrics and GynecologyDaping Hospital and Institute of Surgery ResearchChongqingChina

Personalised recommendations