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
December 2012 Volume 28 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 2012 Volume 28 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
Article

UHRF1 expression is upregulated and associated with cellular proliferation in colorectal cancer

  • Authors:
    • Yasuhide Kofunato
    • Kensuke Kumamoto
    • Katsuharu Saitou
    • Suguru Hayase
    • Hirokazu Okayama
    • Kotaro Miyamoto
    • Yu Sato
    • Kyoko Katakura
    • Izumi Nakamura
    • Shinji Ohki
    • Yoshihisa Koyama
    • Motoko Unoki
    • Seiichi Takenoshita
  • View Affiliations / Copyright

    Affiliations: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan, Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan, Division of Epigenomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan
  • Pages: 1997-2002
    |
    Published online on: September 27, 2012
       https://doi.org/10.3892/or.2012.2064
  • 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

Ubiquitin-like with PHD and ring-finger domain 1 (UHRF1) binds to methylated promoters of a number of tumor-suppressor genes, including p16INK4A and p14ARF, by forming complexes with DNA methyltransferases and HDAC1, resulting in the induction of carcinogenesis. Altered UHRF1 expression has been demonstrated in various types of cancers. Previous reports indicate that UHRF1 expression is regulated by E2F-1 expression. We investigated UHRF1 expression using immunohistochemical staining in 231 colorectal cancer and 40 adenoma specimens, analyzed the relationship between UHRF1 expression and clinicopathological findings and the association between UHRF1 and E2F-1 expression. To better understand the biological function of UHRF1 in colorectal cancer, knockdown of UHRF1 expression was performed using siRNA methods. High UHRF1 expression was observed in 152 of 231 (65.8%) colorectal cancer patients, and was detected in 35 of 40 adenoma specimens samples (87.5%). UHRF1 staining was detected in the nucleus of cancer cells, while it was not detected in colonic normal mucosa. High UHRF1 expression was significantly observed in right compared with left hemicolon cancer (p=0.008). Moreover, high UHRF1 expression tended to be associated with depth of invasion (p=0.051). UHRF1 expression was significantly associated with E2F-1 expression (p<0.0001). Knockdown of UHRF1 expression suppressed cellular growth in colon cancer cell lines, HCT116 and SW620. In conclusion, we demonstrated that UHRF1 expression was upregulated in approximately two-thirds of colorectal cancer specimens and was particularly expressed in right compared with left hemicolon cancer. Moreover, knockdown of UHRF1 expression induced growth inhibition in colon cancer cell lines. UHRF1 may be involved in cellular proliferation and molecular pathogenesis of colorectal cancer in the right hemicolon.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, et al: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 26:2013–2019. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, Donea S, Ludwig H, Schuch G, Stroh C, et al: Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 27:663–671. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, et al: Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 28:4697–4705. 2010. View Article : Google Scholar

4 

Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, et al: K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 359:1757–1765. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Hopfner R, Mousli M, Jeltsch JM, Voulgaris A, Lutz Y, Marin C, Bellocq JP, Oudet P and Bronner C: ICBP90, a novel human CCAAT bonding protein, involved in the regulation of topoisomerase II alpha expression. Cancer Res. 60:121–128. 2000.PubMed/NCBI

6 

Mousli M, Hopfner R, Abbady AQ, Monté D, Jeanblanc M, Oudet P, Louis B and Bronner C: ICBP90 belongs to a new family of proteins with an expression that is deregulated in cancer cells. Br J Cancer. 89:120–127. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Unoki M, Nishidate T and Nakamura Y: ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain. Oncogene. 23:7601–7610. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Unoki M, Daigo Y, Koinuma J, Tsuchiya E, Hamamoto R and Nakamura Y: UHRF1 is a novel diagnostic marker of lung cancer. Br J Cancer. 103:217–222. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Crnogorac-Jurcevic T, Gangeswaran R, Bhakta V, Capurso G, Lattimore S, Akada M, Sunamura M, Prime W, Campbell F, Brentnall TA, et al: Proteomic analysis of chronic pancreatitis and pancreatic adenocarcinoma. Gastroenterology. 129:1454–1463. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Oba-Shinjo SM, Bengtson MH, Winnischofer SM, Colin C, Vedoy CG, de Mendonça Z, Marie SK and Sogayar MC: Identification of novel differentially expressed genes in human astrocytomas by cDNA representational difference analysis. Brain Res Mol Brain Res. 140:25–33. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Lorenzato M, Caudroy S, Bronner C, Evrard G, Simon M, Durlach A, Birembaut P and Clavel C: Cell cycle and/or proliferation markers: what is the best method to discriminate cervical high-grade lesions? Hum Pathol. 36:1101–1107. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Unoki M, Kelly JD, Neal DE, Ponder BA, Nakamura Y and Hamamoto R: UHRF1 is a novel molecular marker for diagnosis and the prognosis of bladder cancer. Br J Cancer. 101:98–105. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Unoki M, Brunet J and Mousli M: Drug discovery targeting epigenetic codes: the great potential of UHRF1, which links DNA methylation and histone modifications, as a drug target in cancers and toxoplasmosis. Biochem Pharmacol. 78:1279–1288. 2009. View Article : Google Scholar

14 

Arima Y, Hirota T, Bronner C, Mousli M, Fujiwara T, Niwa S, Ishikawa H and Saya H: Down-regulation of nuclear protein ICBP90 by p53/p21Cip1/WAF1-dependent DNA-damage checkpoint signals contributes to cell cycle arrest at G1/S transition. Genes Cells. 9:131–142. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Trotzier MA, Bronner C, Bathami K, Mathieu E, Abbady AQ, Jeanblanc M, Muller CD, Rochette-Egly C and Mousli M: Phosphorylation of ICBP90 by protein kinase A enhances topoisomerase II alpha expression. Biochem Biophys Res Commun. 319:590–595. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Bostick M, Kim JK, Estève PO, Clark A, Pradhan S and Jacobsen SE: UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science. 317:1760–1764. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Arita K, Ariyoshi M, Tochio H, Nakamura Y and Shirakawa M: Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism. Nature. 455:818–821. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Avvakumov GV, Walker JR, Xue S, Li Y, Duan S, Bronner C, Arrowsmith CH and Dhe-Paganon S: Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature. 455:822–825. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Hashimoto H, Horton JR, Zhang X, Bostick M, Jacobsen SE and Cheng X: The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix. Nature. 455:826–829. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo TA, Shinga J, Mizutani-Koseki Y, Toyoda T, Okamura K, et al: The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature. 450:908–912. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Kim JK, Estève PO, Jacobsen SE and Pradhan S: UHRF1 binds G9a and participates in p21 transcriptional regulation in mammalian cells. Nucleic Acids Res. 37:493–505. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Jin W, Chen L, Chen Y, Xu SG, Di GH, Yin WJ, Wu J and Shao ZM: UHRF1 is associated with epigenetic silencing of BRCA1 in sporadic breast cancer. Breast Cancer Res Treat. 123:359–373. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Meilinger D, Fellinger K, Bultmann S, Rothbauer U, Bonapace IM, Klinkert WE, Spada F and Leonhardt H: Np95 interacts with de novo DNA methyltransferases, Dnmt3a and Dnmt3b, and mediates epigenetic silencing of the viral CMV promoter in embryonic stem cells. EMBO Rep. 10:1259–1264. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Abbady AQ, Bronner C, Bathami K, Muller CD, Jeanblanc M, Mathieu E, Klein JP, Candolfi E and Mousli M: TCR pathway involves ICBP90 gene down-regulation via E2F binding sites. Biochem Pharmacol. 70:570–579. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Distler P and Holt PR: Are right- and left-sided colon neoplasms distinct tumors? Dig Dis. 15:302–311. 1997. View Article : Google Scholar : PubMed/NCBI

26 

Birkenkamp-Demtroder K, Olesen SH, Sørensen FB, et al: Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid. Gut. 54:374–384. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Elsaleh H, Joseph D, Grieu F, Zeps N, Spry N and Iacopetta B: Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet. 355:1745–1750. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Kapiteijn E, Liefers GJ, Los LC, et al: Mechanisms of oncogenesis in colon versus rectal cancer. J Pathol. 195:171–178. 2001. View Article : Google Scholar : PubMed/NCBI

29 

Fric P, Sovová V, Sloncová E, Lojda Z, Jirásek A and Cermák J: Different expression of some molecular markers in sporadic cancer of the left and right colon. Eur J Cancer Prev. 9:265–268. 2000. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kofunato Y, Kumamoto K, Saitou K, Hayase S, Okayama H, Miyamoto K, Sato Y, Katakura K, Nakamura I, Ohki S, Ohki S, et al: UHRF1 expression is upregulated and associated with cellular proliferation in colorectal cancer. Oncol Rep 28: 1997-2002, 2012.
APA
Kofunato, Y., Kumamoto, K., Saitou, K., Hayase, S., Okayama, H., Miyamoto, K. ... Takenoshita, S. (2012). UHRF1 expression is upregulated and associated with cellular proliferation in colorectal cancer. Oncology Reports, 28, 1997-2002. https://doi.org/10.3892/or.2012.2064
MLA
Kofunato, Y., Kumamoto, K., Saitou, K., Hayase, S., Okayama, H., Miyamoto, K., Sato, Y., Katakura, K., Nakamura, I., Ohki, S., Koyama, Y., Unoki, M., Takenoshita, S."UHRF1 expression is upregulated and associated with cellular proliferation in colorectal cancer". Oncology Reports 28.6 (2012): 1997-2002.
Chicago
Kofunato, Y., Kumamoto, K., Saitou, K., Hayase, S., Okayama, H., Miyamoto, K., Sato, Y., Katakura, K., Nakamura, I., Ohki, S., Koyama, Y., Unoki, M., Takenoshita, S."UHRF1 expression is upregulated and associated with cellular proliferation in colorectal cancer". Oncology Reports 28, no. 6 (2012): 1997-2002. https://doi.org/10.3892/or.2012.2064
Copy and paste a formatted citation
x
Spandidos Publications style
Kofunato Y, Kumamoto K, Saitou K, Hayase S, Okayama H, Miyamoto K, Sato Y, Katakura K, Nakamura I, Ohki S, Ohki S, et al: UHRF1 expression is upregulated and associated with cellular proliferation in colorectal cancer. Oncol Rep 28: 1997-2002, 2012.
APA
Kofunato, Y., Kumamoto, K., Saitou, K., Hayase, S., Okayama, H., Miyamoto, K. ... Takenoshita, S. (2012). UHRF1 expression is upregulated and associated with cellular proliferation in colorectal cancer. Oncology Reports, 28, 1997-2002. https://doi.org/10.3892/or.2012.2064
MLA
Kofunato, Y., Kumamoto, K., Saitou, K., Hayase, S., Okayama, H., Miyamoto, K., Sato, Y., Katakura, K., Nakamura, I., Ohki, S., Koyama, Y., Unoki, M., Takenoshita, S."UHRF1 expression is upregulated and associated with cellular proliferation in colorectal cancer". Oncology Reports 28.6 (2012): 1997-2002.
Chicago
Kofunato, Y., Kumamoto, K., Saitou, K., Hayase, S., Okayama, H., Miyamoto, K., Sato, Y., Katakura, K., Nakamura, I., Ohki, S., Koyama, Y., Unoki, M., Takenoshita, S."UHRF1 expression is upregulated and associated with cellular proliferation in colorectal cancer". Oncology Reports 28, no. 6 (2012): 1997-2002. https://doi.org/10.3892/or.2012.2064
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