Tumor Biology

, Volume 35, Issue 5, pp 4509–4516 | Cite as

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

  • Shuang-Xiang Tan
  • Rui-Cheng Hu
  • Yong-Li Tan
  • Jing-Jing Liu
  • Wen-En Liu
Research Article


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.


PRDM5 Tumor suppressor Lung squamous cell carcinoma Promoter methylation 



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.


  1. 1.
    Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefPubMedGoogle Scholar
  3. 3.
    Brzeziańska E, Dutkowska A, Antczak A. The significance of epigenetic alterations in lung carcinogenesis. Mol Biol Rep. 2013;40:309–25.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 6.
    Wu H, Min J, Lunin VV, Antoshenko T, et al. Structural biology of human H3K9 methyltransferases. PLoS One. 2010;5:e8570.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Fog CK, Galli GG, Lund AH. PRDM proteins: important players in differentiation and disease. Bioessays. 2012;34:50–60.CrossRefPubMedGoogle Scholar
  8. 8.
    Deng Q, Huang S. PRDM5 is silenced in human cancers and has growth suppressive activities. Oncogene. 2004;23:4903–10.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 11.
    Gronbaek K, Hother C, Jones PA. Epigenetic changes in cancer. APMIS. 2007;115:1039–159.CrossRefPubMedGoogle Scholar
  12. 12.
    Khandige S, Shanbhogue VV, Chakrabarty S, Kapettu S. Methylation markers: a potential force driving cancer diagnostics forward. Oncol Res. 2011;19:105–10.CrossRefPubMedGoogle Scholar
  13. 13.
    Van Den Broeck A, Ozenne P, Eymin B, et al. Lung cancer: a modified epigenome. Cell Adh Migr. 2010;4:107–13.CrossRefGoogle Scholar
  14. 14.
    Ding HL, Clouthier DE, Artinger KB. Redundant roles of PRDM family members in zebrafish craniofacial development. Dev Dyn. 2013;242:67–79.CrossRefPubMedGoogle Scholar
  15. 15.
    Hohenauer T, Moore AW. The Prdm family: expanding roles in stem cells and development. Development. 2012;139:2267–82.CrossRefPubMedGoogle Scholar
  16. 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.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Shuang-Xiang Tan
    • 1
  • Rui-Cheng Hu
    • 2
  • Yong-Li Tan
    • 2
  • Jing-Jing Liu
    • 2
  • Wen-En Liu
    • 1
  1. 1.Clinical Laboratory, Xiangya HospitalCentral South UniversityChangshaChina
  2. 2.Department of RespirationHunan Mawangdui HospitalHunan ProvinceChina

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