Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
January-2016 Volume 35 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-2016 Volume 35 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Promoter hypermethylation of PTPL1, PTPN6, DAPK, p16 and 5-azacitidine inhibits growth in DLBCL

  • Authors:
    • Wenming Wang
    • Jing Wang
    • Zhengqian Li
    • Mingxia Zhu
    • Zhe Zhang
    • Yanfang Wang
    • Hongmei Jing
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Peking University Third Hospital, Beijing 100191, P.R. China, Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China, Department of Urology, Peking University Third Hospital, Beijing 100191, P.R. China
  • Pages: 139-146
    |
    Published online on: October 26, 2015
       https://doi.org/10.3892/or.2015.4347
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Aberrant hypermethylation of CpG islands of tumor suppressor is one of the mechanisms for epigenetic loss of gene function. In the present study, the methylation status of the promoter regions of protein tyrosine phosphatase (PTPN) 6, DAPK, and p16 were studied using methylation-specific polymerase chain reaction (MSP) in 26 diffuse large B cell lymphoma (DLBCL) lymphomas. In OCI-LY1 cell line, gene methylation status, expression of PTPL1 and its reactivation by DNA demethylation was determined by PCR and on the protein level by western blotting. ELISA-like reaction was used to detect global DNA methylation measurement. Induction of apoptosis by 5-azacitidine was analyzed by Annexin V/PI staining and flow cytometry. Our results show that hypermethylation of the PTPN6 gene promoter region was found in 15.4% (4/26), the DAPK gene promoter region in 30.8% (8/26), the p16 gene promoter region in 7.7% (2/26). Notably, we identified that PTPL1 was hypermethylated and transcriptionally silenced in OCI-LY1 cell line. The expression of PTPL1 was re-inducible by 5-azacytidine. 5-azacytidine also inhibits the proliferation and decreases the global methylation level of the OCI-LY1 cell line. We can conclude from our study that a higher prevalence of methylation of PTPL1, PTPN6, DAPK and p16 occur in DLBCL. Our data also highlights 5-azacytidine as a potential therapeutic candidate for DLBCL. Further studies are required to substantiate the role of methylation of PTPL1, PTPN6, DAPK and p16 as a marker in diffuse large B cell lymphoma.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H and Jaffe ES: The 2008 WHO classification of lymphoid neoplasms and beyond: Evolving concepts and practical applications. Blood. 117:5019–5032. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Young RM, Shaffer AL III, Phelan JD and Staudt LM: B-cell receptor signaling in diffuse large B-cell lymphoma. Semin Hematol. 52:77–85. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, Klasa R, Savage KJ, Shenkier T, Sutherland J, et al: The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 109:1857–1861. 2007. View Article : Google Scholar

4 

Jiang Y and Melnick A: The epigenetic basis of diffuse large B-cell lymphoma. Semin Hematol. 52:86–96. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Clozel T, Yang S, Elstrom RL, Tam W, Martin P, Kormaksson M, Banerjee S, Vasanthakumar A, Culjkovic B, Scott DW, et al: Mechanism-based epigenetic chemosensitization therapy of diffuse large B-cell lymphoma. Cancer Discov. 3:1002–1019. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Shaknovich R, Geng H, Johnson NA, Tsikitas L, Cerchietti L, Greally JM, Gascoyne RD, Elemento O and Melnick A: DNA methylation signatures define molecular subtypes of diffuse large B-cell lymphoma. Blood. 116:e81–e89. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Robaina MC, Mazzoccoli L, Arruda VO, Reis FR, Apa AG, de Rezende LM and Klumb CE: Deregulation of DNMT1, DNMT3B and miR-29s in Burkitt lymphoma suggests novel contribution for disease pathogenesis. Exp Mol Pathol. 98:200–207. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Zhao X, Yang F, Li S, Liu M, Ying S, Jia X and Wang X: CpG island methylator phenotype of myelodysplastic syndrome identified through genome-wide profiling of DNA methylation and gene expression. Br J Haematol. 165:649–658. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Amara K, Ziadi S, Hachana M, Soltani N, Korbi S and Trimeche M: DNA methyltransferase DNMT3b protein over-expression as a prognostic factor in patients with diffuse large B-cell lymphomas. Cancer Sci. 101:1722–1730. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Freiss G and Chalbos D: PTPN13/PTPL1: An important regulator of tumor aggressiveness. Anticancer Agents Med Chem. 11:78–88. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Castilla C, Chinchón D, Medina R, Torrubia FJ, Japón MA and Sáez C: PTPL1 and PKCδ contribute to proapoptotic signalling in prostate cancer cells. Cell Death Dis. 4:e5762013. View Article : Google Scholar

12 

Glondu-Lassis M, Dromard M, Chavey C, Puech C, Fajas L, Hendriks W and Freiss G: Downregulation of protein tyrosine phosphatase PTP-BL represses adipogenesis. Int J Biochem Cell Biol. 41:2173–2180. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Bodoor K, Haddad Y, Alkhateeb A, Al-Abbadi A, Dowairi M, Magableh A, Bsoul N and Ghabkari A: DNA hypermethylation of cell cycle (p15 and p16) and apoptotic (p14, p53, DAPK and TMS1) genes in peripheral blood of leukemia patients. Asian Pac J Cancer Prev. 15:75–84. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Don KR, Ramani P, Ramshankar V, Sherlin HJ, Premkumar P and Natesan A: Promoter hypermethylation patterns of P16, DAPK and MGMT in oral squamous cell carcinoma: A systematic review and meta-analysis. Indian J Dent Res. 25:797–805. 2014. View Article : Google Scholar

15 

Kupčinskaitė-Noreikienė R, Skiecevičienė J, Jonaitis L, Ugenskienė R, Kupčinskas J, Markelis R, Baltrėnas V, Sakavičius L, Semakina I, Grižas S, et al: CpG island meth-ylation of the MLH1, MGMT, DAPK, and CASP8 genes in cancerous and adjacent noncancerous stomach tissues. Medicina (Kaunas). 49:361–366. 2013.

16 

Zhang Z, Nie F, Kang C, Chen B, Qin Z, Ma J, Ma Y and Zhao X: Increased periostin expression affects the proliferation, collagen synthesis, migration and invasion of keloid fibroblasts under hypoxic conditions. Int J Mol Med. 34:253–261. 2014.PubMed/NCBI

17 

Liang Y, Li Z, Mo N, Li M, Zhuang Z, Wang J, Wang Y and Guo X: Isoflurane preconditioning ameliorates renal ischemia-reperfusion injury through antiinflammatory and antiapoptotic actions in rats. Biol Pharm Bull. 37:1599–1605. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Saleem M, Abbas K, Manan M, Ijaz H, Ahmed B, Ali M, Hanif M, Farooqi AA and Qadir MI: Review - epigenetic therapy for cancer. Pak J Pharm Sci. 28:1023–1032. 2015.PubMed/NCBI

19 

Pike BL, Greiner TC, Wang X, Weisenburger DD, Hsu YH, Renaud G, Wolfsberg TG, Kim M, Weisenberger DJ, Siegmund KD, et al: DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status. Leukemia. 22:1035–1043. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Gibaja V, Shen F, Harari J, Korn J, Ruddy D, Saenz-Vash V, Zhai H, Rejtar T, Paris CG, Yu Z, et al: Development of secondary mutations in wild-type and mutant EZH2 alleles cooperates to confer resistance to EZH2 inhibitors. Oncogene. Apr 20–2015.(Epub ahead of print). http://dx.doi.org/10.1038/onc.2015.114. View Article : Google Scholar : PubMed/NCBI

21 

Wang S and Wang Z: Epigenetic aberrant methylation of tumor suppressor genes in small cell lung cancer. J Thorac Dis. 5:532–537. 2013.PubMed/NCBI

22 

Mehta A, Dobersch S, Romero-Olmedo AJ and Barreto G: Epige-netics in lung cancer diagnosis and therapy. Cancer Metastasis Rev. 34:229–241. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Witzig TE, Hu G, Offer SM, Wellik LE, Han JJ, Stenson MJ, Dogan A, Diasio RB and Gupta M: Epigenetic mechanisms of protein tyrosine phosphatase 6 suppression in diffuse large B-cell lymphoma: Implications for epigenetic therapy. Leukemia. 28:147–154. 2014. View Article : Google Scholar :

24 

Kristensen LS, Treppendahl MB, Asmar F, Girkov MS, Nielsen HM, Kjeldsen TE, Ralfkiaer E, Hansen LL and Grønbæk K: Investigation of MGMT and DAPK1 methylation patterns in diffuse large B-cell lymphoma using allelic MSP-pyrosequencing. Sci Rep. 3:27892013. View Article : Google Scholar : PubMed/NCBI

25 

Koyama M, Oka T, Ouchida M, Nakatani Y, Nishiuchi R, Yoshino T, Hayashi K, Akagi T and Seino Y: Activated proliferation of B-cell lymphomas/leukemias with the SHP1 gene silencing by aberrant CpG methylation. Lab Invest. 83:1849–1858. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Scarfò L and Ghia P: Reprogramming cell death: BCL2 family inhibition in hematological malignancies. Immunol Lett. 155:36–39. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Gupta S and Knowlton AA: HSP60, Bax, apoptosis and the heart. J Cell Mol Med. 9:51–58. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Zeng J, Chen S, Li N, Chen L, Su J, Niu G, Zhu S and Liang Y: Sasanquasaponin from Camellia oleifera Abel. induces apoptosis via Bcl-2, Bax and caspase-3 activation in HepG2 cells. Mol Med Rep. 12:1997–2002. 2015.PubMed/NCBI

29 

Chang C, Swaan PW, Ngo LY, Lum PY, Patil SD and Unadkat JD: Molecular requirements of the human nucleoside transporters hCNT1, hCNT2, and hENT1. Mol Pharmacol. 65:558–570. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Pastor-Anglada M and Pérez-Torras S: Nucleoside transporter proteins as biomarkers of drug responsiveness and drug targets. Front Pharmacol. 6:132015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang W, Wang J, Li Z, Zhu M, Zhang Z, Wang Y and Jing H: Promoter hypermethylation of PTPL1, PTPN6, DAPK, p16 and 5-azacitidine inhibits growth in DLBCL. Oncol Rep 35: 139-146, 2016.
APA
Wang, W., Wang, J., Li, Z., Zhu, M., Zhang, Z., Wang, Y., & Jing, H. (2016). Promoter hypermethylation of PTPL1, PTPN6, DAPK, p16 and 5-azacitidine inhibits growth in DLBCL. Oncology Reports, 35, 139-146. https://doi.org/10.3892/or.2015.4347
MLA
Wang, W., Wang, J., Li, Z., Zhu, M., Zhang, Z., Wang, Y., Jing, H."Promoter hypermethylation of PTPL1, PTPN6, DAPK, p16 and 5-azacitidine inhibits growth in DLBCL". Oncology Reports 35.1 (2016): 139-146.
Chicago
Wang, W., Wang, J., Li, Z., Zhu, M., Zhang, Z., Wang, Y., Jing, H."Promoter hypermethylation of PTPL1, PTPN6, DAPK, p16 and 5-azacitidine inhibits growth in DLBCL". Oncology Reports 35, no. 1 (2016): 139-146. https://doi.org/10.3892/or.2015.4347
Copy and paste a formatted citation
x
Spandidos Publications style
Wang W, Wang J, Li Z, Zhu M, Zhang Z, Wang Y and Jing H: Promoter hypermethylation of PTPL1, PTPN6, DAPK, p16 and 5-azacitidine inhibits growth in DLBCL. Oncol Rep 35: 139-146, 2016.
APA
Wang, W., Wang, J., Li, Z., Zhu, M., Zhang, Z., Wang, Y., & Jing, H. (2016). Promoter hypermethylation of PTPL1, PTPN6, DAPK, p16 and 5-azacitidine inhibits growth in DLBCL. Oncology Reports, 35, 139-146. https://doi.org/10.3892/or.2015.4347
MLA
Wang, W., Wang, J., Li, Z., Zhu, M., Zhang, Z., Wang, Y., Jing, H."Promoter hypermethylation of PTPL1, PTPN6, DAPK, p16 and 5-azacitidine inhibits growth in DLBCL". Oncology Reports 35.1 (2016): 139-146.
Chicago
Wang, W., Wang, J., Li, Z., Zhu, M., Zhang, Z., Wang, Y., Jing, H."Promoter hypermethylation of PTPL1, PTPN6, DAPK, p16 and 5-azacitidine inhibits growth in DLBCL". Oncology Reports 35, no. 1 (2016): 139-146. https://doi.org/10.3892/or.2015.4347
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team