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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
December-2020 Volume 20 Issue 6

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
December-2020 Volume 20 Issue 6

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

  • Supplementary Files
    • Supplementary_Data.pdf
Article

MBD2 and EZH2 regulate the expression of SFRP1 without affecting its methylation status in a colorectal cancer cell line

  • Authors:
    • Jun Yu
    • Yang Xie
    • Yuting Liu
    • Feng Wang
    • Mengying Li
    • Jian Qi
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
  • Article Number: 242
    |
    Published online on: October 22, 2020
       https://doi.org/10.3892/etm.2020.9372
  • 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

Secreted frizzled‑related protein 1 (SFRP1), which is an extracellular inhibitor involved in Wnt signalling, is downregulated by promoter hypermethylation in the early stages of colorectal tumorigenesis. Polycomb  (PCG) and methyl‑CpG‑binding domain (MBD) proteins that serve a role in epigenetic gene regulation. The aim of the present study was to determine the role of PCG and MBD proteins in the regulation of SFRP1 gene expression in colorectal cancer (CRC), specifically in CRC cell lines and the human embryo intestinal mucosa cell line CCC‑HIE‑2. The methylation status of the SFRP1 gene promoter were analysed using methylation‑specific PCR (MSP), whereas SFRP1 mRNA expression was analysed using reverse transcription‑quantitative PCR. The association between PCG and MBD proteins and the SFRP1 gene was assessed, where associated proteins were screened by chromatin immunoprecipitation and their expression were subsequently knocked down using RNA interference to determine their role in the regulation of SFRP1 gene expression. The SFRP1 promoter was demonstrated to be hypermethylated in CRC cell lines and partially methylated in the non‑cancerous cell line CCC‑HIE‑2. SFRP1 mRNA expression was significantly lower in CRC cell lines compared with that of CCC‑HIE‑2 cells. The expression of PCGs enhancer of zeste homolog 2 (EZH2) and BMI1, along with MBD2, was indicated to be upregulated with SFRP1 methylation in HCT116 and SW480 cells. The SFRP1 promoter region was enriched with EZH2 in CCC‑HIE‑2 cells and enriched with EZH2 and MBD2 in SW480 cells, whereas none of the proteins examined were indicated on the SFRP1 promoter in HCT116 cells. The expression of SFRP1 was reactivated by MBD2 small interfering (si)RNA but not by EZH2 siRNA in SW480 cells, but combined MBD2 and EZH2 knockdown effectively restored SFRP1 gene expression without affecting the methylation status of the SFRP1 promoter. In conclusion, data from the present study revealed that MBD2 and EZH2 regulated SFRP1 expression without affecting the hypermethylation of SFRP1 in CRC cell lines. Instead, the regulation of SFRP1 expression may be through a distinct mechanism, which warrants further investigation.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Siegel R, Desantis C and Jemal A: Colorectal cancer statistics, 2014. CA Cancer J Clin. 64:104–117. 2014.PubMed/NCBI View Article : Google Scholar

2 

Vermeulen L, De Sousa E Melo F, van der Heijden M, Cameron K, de Jong JH, Borovski T, Tuynman JB, Todaro M, Merz C, Rodermond H, et al: Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol. 12:468–476. 2010.PubMed/NCBI View Article : Google Scholar

3 

Jensen M, Hoerndli FJ, Brockie PJ, Wang R, Johnson E, Maxfield D, Francis MM, Madsen DM and Maricq AV: Wnt signaling regulates acetylcholine receptor translocation and synaptic plasticity in the adult nervous system. Cell. 149:173–187. 2012.PubMed/NCBI View Article : Google Scholar

4 

Lv C, Li F, Li X, Tian Y, Zhang Y, Sheng X, Song Y, Meng Q, Yuan S, Luan L, et al: MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists. Nat Commun. 8(1036)2017.PubMed/NCBI View Article : Google Scholar

5 

Russell JO and Monga SS: Wnt/β-catenin signaling in liver development, homeostasis, and pathobiology. Annu Rev Pathol. 13:351–378. 2018.PubMed/NCBI View Article : Google Scholar

6 

Tammela T, Sanchez-Rivera FJ, Cetinbas NM, Wu K, Joshi NS, Helenius K, Park Y, Azimi R, Kerper NR, Wesselhoeft RA, et al: A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma. Nature. 545:355–359. 2017.PubMed/NCBI View Article : Google Scholar

7 

Klaus A and Birchmeier W: Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 8:387–398. 2008.PubMed/NCBI View Article : Google Scholar

8 

Rattner A, Hsieh JC, Smallwood PM, Gilbert DJ, Copeland NG, Jenkins NA and Nathans J: A family of secreted proteins contains homology to the cysteine-rich ligand-binding domain of frizzled receptors. Natl Acad Sci USA. 94:2859–2863. 1997.PubMed/NCBI View Article : Google Scholar

9 

Suzuki H, Watkins DN, Jair KW, Schuebel KE, Markowitz SD, Chen WD, Pretlow TP, Yang B, Akiyama Y, Van Engeland M, et al: Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet. 36:417–422. 2004.PubMed/NCBI View Article : Google Scholar

10 

Elzi DJ, Song MH, Hakala K, Weintraub ST and Shiio Y: Wnt antagonist SFRP1 functions as a secreted mediator of senescence. Mol Cell Biol. 32:4388–4399. 2012.PubMed/NCBI View Article : Google Scholar

11 

Qi J, Zhu YQ, Luo J and Tao WH: Hypermethylation and expression regulation of secreted frizzled-related protein genes in colorectal tumor. World J Gastroenterol. 12:7113–7117. 2006.PubMed/NCBI View Article : Google Scholar

12 

Margueron R and Reinberg D: Chromatin structure and the inheritance of epigenetic information. Nat Rev Genet. 11:285–296. 2010.PubMed/NCBI View Article : Google Scholar

13 

Allis CD and Jenuwein T: The molecular hallmarks of epigenetic control. Nat Rev Genet. 17:487–500. 2016.PubMed/NCBI View Article : Google Scholar

14 

Hughes TR and Lambert SA: Transcription factors read epigenetics. Science. 356:489–490. 2017.PubMed/NCBI View Article : Google Scholar

15 

Riising EM, Comet I, Leblanc B, Wu X, Johansen JV and Helin K: Gene silencing triggers polycomb repressive complex 2 recruitment to CpG islands genome wide. Mol Cell. 55:347–360. 2014.PubMed/NCBI View Article : Google Scholar

16 

Pan H, Bilinovich SM, Kaur P, Riehn R, Wang H and Williams DC Jr: CpG and methylation-dependent DNA binding and dynamics of the methylcytosine binding domain 2 protein at the single-molecule level. Nucleic Acids Res. 45:9164–9177. 2017.PubMed/NCBI View Article : Google Scholar

17 

Negishi M, Saraya A, Miyagi S, Nagao K, Inagaki Y, Nishikawa M, Tajima S, Koseki H, Tsuda H, Takasaki Y, et al: Bmi1 cooperates with Dnmt1-associated protein 1 in gene silencing. Biochem Biophys Res Commun. 353:992–998. 2007.PubMed/NCBI View Article : Google Scholar

18 

Wood KH and Zhou Z: Emerging molecular and biological functions of MBD2, a reader of DNA methylation. Fron Genet. 7(93)2016.PubMed/NCBI View Article : Google Scholar

19 

Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van Eynde A, Bernard D, Vanderwinden JM, et al: The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 439:871–874. 2006.PubMed/NCBI View Article : Google Scholar

20 

Ahmed D, Eide PW, Eilertsen IA, Danielsen SA, Eknæs M, Hektoen M, Lind GE and Lothe RA: Epigenetic and genetic features of 24 colon cancer cell lines. Oncogenesis. 2(e71)2013.PubMed/NCBI View Article : Google Scholar

21 

Bai J, Xu J, Zhao J and Zhang R: lncRNA SNHG1 cooperated with miR-497/miR-195-5p to modify epithelial-mesenchymal transition underlying colorectal cancer exacerbation. J Cell Physiol. 235:1453–1468. 2020.PubMed/NCBI View Article : Google Scholar

22 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

23 

Cruciat CM and Niehrs C: Secreted and transmembrane wnt inhibitors and activators. Cold Spring Harb Perspect Biol. 5(a015081)2013.PubMed/NCBI View Article : Google Scholar

24 

Yu J, Xie Y, Li M, Zhou F, Zhong Z, Liu Y, Wang F and Qi J: Association between SFRP promoter hypermethylation and different types of cancer: A systematic review and meta-analysis. Oncol Lett. 18:3481–3492. 2019.PubMed/NCBI View Article : Google Scholar

25 

Tatematsu KI, Yamazaki T and Ishikawa F: MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase. Genes Cells. 5:677–688. 2000.PubMed/NCBI View Article : Google Scholar

26 

Jones PA and Taylor SM: Cellular differentiation, cytidine analogues and DNA methylation. Cell. 20:85–93. 1980.PubMed/NCBI View Article : Google Scholar

27 

Cramer JM, Scarsdale JN, Walavalkar NM, Buchwald WA, Ginder GD and Williams DC Jr: Probing the dynamic distribution of bound states for methylcytosine-binding domains on DNA. J Biol Chem. 289:1294–1302. 2014.PubMed/NCBI View Article : Google Scholar

28 

Wood KH and Zhou Z: Emerging molecular and biological functions of MBD2, a reader of DNA methylation. Front Genet. 7(93)2016.PubMed/NCBI View Article : Google Scholar

29 

Quan H, Zhou F, Nie D, Chen Q, Cai X, Shan X, Zhou Z, Chen K, Huang A, Li S and Tang N: Hepatitis C virus core protein epigenetically silences SFRP1 and enhances HCC aggressiveness by inducing epithelial-mesenchymal transition. Oncogene. 33:2826–2835. 2014.PubMed/NCBI View Article : Google Scholar

30 

Desai MA, Webb HD, Sinanan LM, Scarsdale JN, Walavalkar NM, Ginder GD and Williams DC Jr: An intrinsically disordered region of methyl-CpG binding domain protein 2 (MBD2) recruits the histone deacetylase core of the NuRD complex. Nucleic Acids Res. 43:3100–3113. 2015.PubMed/NCBI View Article : Google Scholar

31 

Berger J and Bird A: Role of MBD2 in gene regulation and tumorigenesis. Biochem Soc Trans. 33:1537–1540. 2005.PubMed/NCBI View Article : Google Scholar

32 

Tuğrul M, Paixão T, Barton NH and Tkačik G: Dynamics of transcription factor binding site evolution. PLoS Genet. 11(e1005639)2015.PubMed/NCBI View Article : Google Scholar

33 

Liu Y, Toh H, Sasaki H, Zhang X and Cheng X: An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence. Genes Dev. 26:2374–2379. 2012.PubMed/NCBI View Article : Google Scholar

34 

Yin Y, Morgunova E, Jolma A, Kaasinen E, Sahu B, Khund-Sayeed S, Das PK, Kivioja T, Dave K, Zhong F, et al: Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science. 356(eaaj2239)2017.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yu J, Xie Y, Liu Y, Wang F, Li M and Qi J: MBD2 and EZH2 regulate the expression of SFRP1 without affecting its methylation status in a colorectal cancer cell line. Exp Ther Med 20: 242, 2020.
APA
Yu, J., Xie, Y., Liu, Y., Wang, F., Li, M., & Qi, J. (2020). MBD2 and EZH2 regulate the expression of SFRP1 without affecting its methylation status in a colorectal cancer cell line. Experimental and Therapeutic Medicine, 20, 242. https://doi.org/10.3892/etm.2020.9372
MLA
Yu, J., Xie, Y., Liu, Y., Wang, F., Li, M., Qi, J."MBD2 and EZH2 regulate the expression of SFRP1 without affecting its methylation status in a colorectal cancer cell line". Experimental and Therapeutic Medicine 20.6 (2020): 242.
Chicago
Yu, J., Xie, Y., Liu, Y., Wang, F., Li, M., Qi, J."MBD2 and EZH2 regulate the expression of SFRP1 without affecting its methylation status in a colorectal cancer cell line". Experimental and Therapeutic Medicine 20, no. 6 (2020): 242. https://doi.org/10.3892/etm.2020.9372
Copy and paste a formatted citation
x
Spandidos Publications style
Yu J, Xie Y, Liu Y, Wang F, Li M and Qi J: MBD2 and EZH2 regulate the expression of SFRP1 without affecting its methylation status in a colorectal cancer cell line. Exp Ther Med 20: 242, 2020.
APA
Yu, J., Xie, Y., Liu, Y., Wang, F., Li, M., & Qi, J. (2020). MBD2 and EZH2 regulate the expression of SFRP1 without affecting its methylation status in a colorectal cancer cell line. Experimental and Therapeutic Medicine, 20, 242. https://doi.org/10.3892/etm.2020.9372
MLA
Yu, J., Xie, Y., Liu, Y., Wang, F., Li, M., Qi, J."MBD2 and EZH2 regulate the expression of SFRP1 without affecting its methylation status in a colorectal cancer cell line". Experimental and Therapeutic Medicine 20.6 (2020): 242.
Chicago
Yu, J., Xie, Y., Liu, Y., Wang, F., Li, M., Qi, J."MBD2 and EZH2 regulate the expression of SFRP1 without affecting its methylation status in a colorectal cancer cell line". Experimental and Therapeutic Medicine 20, no. 6 (2020): 242. https://doi.org/10.3892/etm.2020.9372
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