Skip to main content

Advertisement

SpringerLink
Log in

Promoter methylation-mediated downregulation of PRDM5 contributes to the development of lung squamous cell carcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

PRDM5 has been proposed as a tumor suppressor frequently downregualted in tumor. In this study, lung squamous cell carcinoma tissues and adjacent nontumorous normal tissues were collected from 30 patients. PRDM5 expression was detected by reverse transcription polymerase chain reaction and Western blot analysis, DNA methylation of PRDM5 promoter was analyzed by methylation-specific PCR. SK-MES-1 cells or xenografts in nude mice were treated with 5-aza-2′-deoxycitydine, and cell proliferation and tumor growth in nude mice were examined. We found that PRDM5 promoter was methylated and PRDM5 expression at both mRNA and protein levels was reduced in lung squamous cell carcinoma tissues. Furthermore, PRDM5 promoter methylation was significantly correlated with tumor differentiation and lymph node metastasis of lung squamous cell carcinoma, but not with age, gender, smoking, or tumor grade. 5-aza-2′-deoxycitydine inhibited the proliferation of SK-MES-1 cells and the growth of xenografts in nude mice, accompanied by reduced methylation of PRDM5 promoter and increased expression of PRDM5. Taken together, our data suggest that PRDM5 is a tumor suppressor in lung cancer and is a promising target for the diagnosis, prognosis, and therapy of lung squamous cell carcinoma.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Drilon A, Rekhtman N, Ladanyi M, Paik P. Squamous-cell carcinomas of the lung: emerging biology, controversies, and the promise of targeted therapy. Lancet Oncol. 2012;13:e418–26.

    Article  CAS  PubMed  Google Scholar 

  3. Brzeziańska E, Dutkowska A, Antczak A. The significance of epigenetic alterations in lung carcinogenesis. Mol Biol Rep. 2013;40:309–25.

    Article  PubMed  Google Scholar 

  4. Zhang Y, Xu R, Li G, Xie X, Long J, Wang H. Loss of expression of the differentially expressed in adenocarcinoma of the lung (DAL-1) protein is associated with metastasis of non-small cell lung carcinoma cells. Tumour Biol. 2012;33:1915–25.

    Article  PubMed  Google Scholar 

  5. Yu Y, Yin D, Hoque MO, Cao B, Jia Y, Yang Y, et al. AKT signaling pathway activated by HIN-1 methylation in non-small cell lung cancer. Tumour Biol. 2012;33:307–14.

    Article  CAS  PubMed  Google Scholar 

  6. Wu H, Min J, Lunin VV, Antoshenko T, et al. Structural biology of human H3K9 methyltransferases. PLoS One. 2010;5:e8570.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Fog CK, Galli GG, Lund AH. PRDM proteins: important players in differentiation and disease. Bioessays. 2012;34:50–60.

    Article  CAS  PubMed  Google Scholar 

  8. Deng Q, Huang S. PRDM5 is silenced in human cancers and has growth suppressive activities. Oncogene. 2004;23:4903–10.

    Article  CAS  PubMed  Google Scholar 

  9. Cheng HY, Chen XW, Cheng L, et al. DNA methylation and carcinogenesis of PRDM5 in cervical cancer. J Cancer Res Clin Oncol. 2010;136:1821–5.

    Article  CAS  PubMed  Google Scholar 

  10. Watanabe Y, Toyota M, Kondo Y, et al. PRDM5 identified as a target of epigenetic silencing in colorectal and gastric cancer. Clin Cancer Res. 2007;13:4786–94.

    Article  CAS  PubMed  Google Scholar 

  11. Gronbaek K, Hother C, Jones PA. Epigenetic changes in cancer. APMIS. 2007;115:1039–159.

    Article  PubMed  Google Scholar 

  12. Khandige S, Shanbhogue VV, Chakrabarty S, Kapettu S. Methylation markers: a potential force driving cancer diagnostics forward. Oncol Res. 2011;19:105–10.

    Article  PubMed  Google Scholar 

  13. Van Den Broeck A, Ozenne P, Eymin B, et al. Lung cancer: a modified epigenome. Cell Adh Migr. 2010;4:107–13.

    Article  Google Scholar 

  14. Ding HL, Clouthier DE, Artinger KB. Redundant roles of PRDM family members in zebrafish craniofacial development. Dev Dyn. 2013;242:67–79.

    Article  CAS  PubMed  Google Scholar 

  15. Hohenauer T, Moore AW. The Prdm family: expanding roles in stem cells and development. Development. 2012;139:2267–82.

    Article  CAS  PubMed  Google Scholar 

  16. Kinameri E, Inoue T, Aruga J, et al. Prdm proto-oncogene transcription factor family expression and interaction with the Notch-Hes pathway in mouse neurogenesis. PLoS One. 2008;3:e3859.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was supported by the Natural Science Foundation of Hunan Province (no. 11JJ310).

Conflict of interest

The authors declared that they have no conflict of interests.

Author information

Authors and Affiliations

  1. Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China

    Shuang-Xiang Tan & Wen-En Liu

  2. Department of Respiration, Hunan Mawangdui Hospital, 410016, Hunan Province, China

    Rui-Cheng Hu, Yong-Li Tan & Jing-Jing Liu

Authors
  1. Shuang-Xiang Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rui-Cheng Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yong-Li Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jing-Jing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wen-En Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wen-En Liu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tan, SX., Hu, RC., Tan, YL. et al. Promoter methylation-mediated downregulation of PRDM5 contributes to the development of lung squamous cell carcinoma. Tumor Biol. 35, 4509–4516 (2014). https://doi.org/10.1007/s13277-013-1593-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-013-1593-2

Keywords

Search

Navigation