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Article

Regulation of the expression of claudin 23 by the enhancer of zeste 2 polycomb group protein in colorectal cancer

  • Authors:
    • Natalia Maryan
    • Malgorzata Statkiewicz
    • Michal Mikula
    • Krzysztof Goryca
    • Agnieszka Paziewska
    • Adriana Strzałkowska
    • Michalina Dabrowska
    • Mateusz Bujko
    • Jerzy Ostrowski
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Maria Sklodowska‑Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02‑781, Poland, Department of Genetics, Maria Sklodowska‑Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02‑781, Poland, Department of Molecular and Translational Oncology, Maria Sklodowska‑Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02‑781, Poland
  • Pages: 728-736
    |
    Published online on: February 19, 2015
       https://doi.org/10.3892/mmr.2015.3378
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Abstract

Altered epigenetic mechanisms, similar to gene mutations, contribute to the pathogenesis and molecular heterogeneity of neoplasms, including colorectal cancer (CRC). Enhancer of zeste 2 (EZH2) is a histone methyltransferase, which is involved in epigenetic gene silencing and is aberrantly expressed in CRC. Therefore, the identification of the genes regulated by EZH2 in CRC is important to improve current understanding of its role in cancer epigenetics. The present study used chromatin immunoprecipitation (ChIP) followed by deep sequencing to assess genome‑wide EZH2‑DNA interactions in healthy or CRC mucosa samples. In total, 86.9/61.6 and 92.5/62.6 million tags were sequenced/mapped in healthy and CRC mucosa samples, respectively. The EZH2‑binding densities were correlated with transcriptomic datasets and this demonstrated that the claudin‑23 (CLDN23) gene, which encodes a component of cell‑cell adhesion structures, was occupied by EZH2 and significantly silenced in CRC tissue. The measurement of DNA methylation at the CLDN23 promoter using pyrosequencing excluded the possibility that silencing of this gene in CRC patient samples was a result of DNA hypermethylation. Following treatment of the Colo205 and HT‑29 CRC cell lines, with the EZH2 inhibitor, GSK126, the level of histone H3 lysine 27 trimethylation (H3K27me3) was reduced and the mRNA and protein expression levels of CLDN23 were increased. ChIP analysis confirmed that the level of H3K27m3 along the CLDN23 gene was decreased in the GSK126‑treated cell lines. Furthermore, ChIP analysis of these samples detected histone H3 lysine 4 trimethylation (H3K4me3) at the CLDN23 promoter, demonstrating that the balance between H3K27me3 and H3K4me3 may underlie the regulation of the expression of CLDN23. The present study demonstrated an epigenetic link between the activity of the EZH2 methyltransferase at the CLDN23 locus and the expression of CLDN23 in CRC tissue.
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View References

1 

Di Croce L and Helin K: Transcriptional regulation by Polycomb group proteins. Nat Struct Mol Biol. 20:1147–1155. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Chang CJ and Hung MC: The role of EZH2 in tumour progression. Br J Cancer. 106:243–247. 2012. View Article : Google Scholar :

3 

Forbes MS: Cell Structure. Cell Physiology Source Book. 4th. Sperelakis N: Academic Press; San Diego, CA: pp. 67–83. 2012

4 

Ding L, Lu Z, Lu Q and Chen YH: The claudin family of proteins in human malignancy: a clinical perspective. Cancer Manag Res. 5:367–375. 2013.PubMed/NCBI

5 

Findley MK and Koval M: Regulation and roles for claudin family tight junction proteins. IUBMB Life. 61:431–437. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Günzel D and Yu ASL: Claudins and the modulation of tight junction permeability. Physiol Rev. 93:525–569. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Turksen K and Troy TC: Junctions gone bad: claudins and loss of the barrier in cancer. Biochim Biophys Acta. 1816:73–79. 2011.PubMed/NCBI

8 

Valle BL and Morin PJ: Claudins in Cancer Biology. Current Topics in Membranes. Yu ASL: 65. Academic Press; Amsterdam: pp. 293–333. 2010

9 

Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Frixen UH, Behrens J, Sachs M, et al: E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 113:173–185. 1991. View Article : Google Scholar : PubMed/NCBI

11 

Hirohashi S and Kanai Y: Cell adhesion system and human cancer morphogenesis. Cancer Sci. 94:575–581. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Skrzypczak M, Goryca K, Rubel T, et al: Modeling oncogenic signaling in colon tumors by multidirectional analyses of microarray data directed for maximization of analytical reliability. PLoS One. 5:e130912010. View Article : Google Scholar : PubMed/NCBI

13 

Mikula M, Rubel T, Karczmarski J, Goryca K, Dadlez M and Ostrowski J: Integrating proteomic and transcriptomic high-throughput surveys for search of new biomarkers of colon tumors. Funct Integr Genomics. 11:215–224. 2011. View Article : Google Scholar

14 

Flanagin S, Nelson JD, Castner DG, Denisenko O and Bomsztyk K: Microplate-based chromatin immunoprecipitation method, Matrix ChIP: a platform to study signaling of complex genomic events. Nucleic Acids Res. 36:e172008. View Article : Google Scholar : PubMed/NCBI

15 

Yu J, Feng Q, Ruan Y, Komers R, Kiviat N and Bomsztyk K: Microplate-based platform for combined chromatin and DNA methylation immunoprecipitation assays. BMC Mol Biol. 12:492011. View Article : Google Scholar : PubMed/NCBI

16 

Mikula M, Bomsztyk K, Goryca K, Chojnowski K and Ostrowski J: Heterogeneous nuclear ribonucleoprotein (HnRNP) K genome-wide binding survey reveals its role in regulating 3′-end RNA processing and transcription termination at the early growth response 1 (EGR1) gene through XRN2 exonuclease. J Biol Chem. 288:24788–24798. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Aird D, Ross MG, Chen W-S, et al: Analyzing and minimizing PCR amplification bias in Illumina sequencing libraries. Genome Biol. 12:R182011. View Article : Google Scholar : PubMed/NCBI

18 

Langmead B, Trapnell C, Pop M and Salzberg SL: Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10:R252009. View Article : Google Scholar : PubMed/NCBI

19 

Zhang Y, Liu T, Meyer CA, et al: Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9:R1372008. View Article : Google Scholar : PubMed/NCBI

20 

Kent WJ, Sugnet CW, Furey TS, et al: The human genome browser at UCSC. Genome Res. 12:996–1006. 2002.doi: 10.1101/gr.229102.Article published online before print in May 2002. PubMed/NCBI

21 

ENCODE Project Consortium: An integrated encyclopedia of DNA elements in the human genome. Nature. 489:57–74. 2012. View Article : Google Scholar : PubMed/NCBI

22 

McCabe MT, Ott HM, Ganji G, et al: EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature. 492:108–112. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Mikula M, Gaj P, Dzwonek K, et al: Comprehensive analysis of the palindromic motif TCTCGCGAGA: a regulatory element of the HNRNPK promoter. DNA Res. 17:245–260. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Singh AB, Sharma A and Dhawan P: Claudin family of proteins and cancer: an overview. J Oncol. 2010:2010. View Article : Google Scholar : PubMed/NCBI

25 

Chi P, Allis CD and Wang GG: Covalent histone modifications - miswritten, misinterpreted and mis-erased in human cancers. Nat Rev Cancer. 10:457–469. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Bernstein BE, Mikkelsen TS, Xie X, et al: A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 125:315–326. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Larson JL and Yuan GC: Chromatin states accurately classify cell differentiation stages. PLoS One. 7:e314142012. View Article : Google Scholar : PubMed/NCBI

28 

Rodriguez J, Muñoz M, Vives L, Frangou CG, Groudine M and Peinado MA: Bivalent domains enforce transcriptional memory of DNA methylated genes in cancer cells. Proc Natl Acad Sci USA. 105:19809–19814. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Voigt P, Tee WW and Reinberg D: A double take on bivalent promoters. Genes Dev. 27:1318–1338. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Mikkelsen TS, Ku M, Jaffe DB, et al: Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature. 448:553–560. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Ku M, Koche RP, Rheinbay E, et al: Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genet. 4:e10002422008. View Article : Google Scholar : PubMed/NCBI

32 

Brookes E, de Santiago I, Hebenstreit D, et al: Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs. Cell Stem Cell. 10:157–170. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Kwon MJ, Kim SH, Jeong HM, et al: Claudin-4 overexpression is associated with epigenetic derepression in gastric carcinoma. Lab Invest. 91:1652–1667. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Kwon MJ, Kim SS, Choi YL, et al: Derepression of CLDN3 and CLDN4 during ovarian tumorigenesis is associated with loss of repressive histone modifications. Carcinogenesis. 31:974–983. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Katoh M and Katoh M: CLDN23 gene, frequently down-regulated in intestinal-type gastric cancer, is a novel member of CLAUDIN gene family. Int J Mol Med. 11:683–689. 2003.PubMed/NCBI

36 

Pitule P, Vycital O, Bruha J, et al: Differential expression and prognostic role of selected genes in colorectal cancer patients. Anticancer Res. 33:4855–4865. 2013.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Maryan N, Statkiewicz M, Mikula M, Goryca K, Paziewska A, Strzałkowska A, Dabrowska M, Bujko M and Ostrowski J: Regulation of the expression of claudin 23 by the enhancer of zeste 2 polycomb group protein in colorectal cancer. Mol Med Rep 12: 728-736, 2015.
APA
Maryan, N., Statkiewicz, M., Mikula, M., Goryca, K., Paziewska, A., Strzałkowska, A. ... Ostrowski, J. (2015). Regulation of the expression of claudin 23 by the enhancer of zeste 2 polycomb group protein in colorectal cancer. Molecular Medicine Reports, 12, 728-736. https://doi.org/10.3892/mmr.2015.3378
MLA
Maryan, N., Statkiewicz, M., Mikula, M., Goryca, K., Paziewska, A., Strzałkowska, A., Dabrowska, M., Bujko, M., Ostrowski, J."Regulation of the expression of claudin 23 by the enhancer of zeste 2 polycomb group protein in colorectal cancer". Molecular Medicine Reports 12.1 (2015): 728-736.
Chicago
Maryan, N., Statkiewicz, M., Mikula, M., Goryca, K., Paziewska, A., Strzałkowska, A., Dabrowska, M., Bujko, M., Ostrowski, J."Regulation of the expression of claudin 23 by the enhancer of zeste 2 polycomb group protein in colorectal cancer". Molecular Medicine Reports 12, no. 1 (2015): 728-736. https://doi.org/10.3892/mmr.2015.3378
Copy and paste a formatted citation
x
Spandidos Publications style
Maryan N, Statkiewicz M, Mikula M, Goryca K, Paziewska A, Strzałkowska A, Dabrowska M, Bujko M and Ostrowski J: Regulation of the expression of claudin 23 by the enhancer of zeste 2 polycomb group protein in colorectal cancer. Mol Med Rep 12: 728-736, 2015.
APA
Maryan, N., Statkiewicz, M., Mikula, M., Goryca, K., Paziewska, A., Strzałkowska, A. ... Ostrowski, J. (2015). Regulation of the expression of claudin 23 by the enhancer of zeste 2 polycomb group protein in colorectal cancer. Molecular Medicine Reports, 12, 728-736. https://doi.org/10.3892/mmr.2015.3378
MLA
Maryan, N., Statkiewicz, M., Mikula, M., Goryca, K., Paziewska, A., Strzałkowska, A., Dabrowska, M., Bujko, M., Ostrowski, J."Regulation of the expression of claudin 23 by the enhancer of zeste 2 polycomb group protein in colorectal cancer". Molecular Medicine Reports 12.1 (2015): 728-736.
Chicago
Maryan, N., Statkiewicz, M., Mikula, M., Goryca, K., Paziewska, A., Strzałkowska, A., Dabrowska, M., Bujko, M., Ostrowski, J."Regulation of the expression of claudin 23 by the enhancer of zeste 2 polycomb group protein in colorectal cancer". Molecular Medicine Reports 12, no. 1 (2015): 728-736. https://doi.org/10.3892/mmr.2015.3378
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