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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
February 2013 Volume 42 Issue 2

Full Size Image

Cover Legend PDF

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
February 2013 Volume 42 Issue 2

Full Size Image

Cover Legend PDF

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 Open Access

Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma

  • Authors:
    • Osamu Dohi
    • Kohichiroh Yasui
    • Yasuyuki Gen
    • Hisashi Takada
    • Mio Endo
    • Kazuhiro Tsuji
    • Chika Konishi
    • Nobuhisa Yamada
    • Hironori Mitsuyoshi
    • Nobuaki Yagi
    • Yuji Naito
    • Shinji Tanaka
    • Shigeki Arii
    • Toshikazu Yoshikawa
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan, Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
    Copyright: © Dohi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 411-418
    |
    Published online on: November 30, 2012
       https://doi.org/10.3892/ijo.2012.1724
  • 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

MicroRNAs (miRNAs) are small non-coding RNAs that function as endogenous silencers of target genes. Some tumor-suppressive miRNAs are known to be epigenetically silenced by promoter DNA methylation in cancer. In the present study, we aimed to identify miRNA genes that are silenced by DNA hypermethylation in hepatocellular carcinoma (HCC). We screened for miRNA genes with promoter DNA hypermethylation using a genome-wide methylation microarray analysis in HCC cells. It was found that miR-335, which is harbored within an intron of its protein-coding host gene, MEST, was downregulated by aberrant promoter hypermethylation via further methylation assays, including methylation-specific PCR, combined bisulfite and restriction analysis, bisulfite sequencing analysis and 5-aza-2'-deoxycytidine treatment. The expression levels of miR-335 significantly correlated with those of MEST, supporting the notion that the intronic miR-335 is co-expressed with its host gene. The levels of miR-335/MEST methylation were significantly higher in 18 (90%) out of 20 primary HCC tumors, compared to their non-tumor tissue counterparts (P<0.001). The expression levels of miR-335 were significantly lower in 25 (78%) out of 32 primary HCC tumors, compared to their non-tumor tissue counterparts (P=0.001). Furthermore, the expression levels of miR-335 were significantly lower in HCC tumors with distant metastasis compared to those without distant metastasis (P=0.02). In conclusion, our results indicate that expression of miR-335 is reduced by aberrant DNA methylation in HCC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1. 

Bosch FX, Ribes J, Cléries R and Díaz M: Epidemiology of hepatocellular carcinoma. Clin Liver Dis. 9:191–211. 2005. View Article : Google Scholar : PubMed/NCBI

2. 

Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI

3. 

Bartel DP: MicroRNAs: genomics, biogenesis, mechanism and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI

4. 

He L and Hannon GJ: MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 5:522–531. 2004. View Article : Google Scholar : PubMed/NCBI

5. 

Xu P, Guo M and Hay BA: MicroRNAs and the regulation of cell death. Trends Genet. 20:617–624. 2004. View Article : Google Scholar

6. 

Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F and Croce CM: Frequent deletions and downregulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 99:15524–15529. 2002. View Article : Google Scholar : PubMed/NCBI

7. 

Michael MZ, SM OC, van Holst Pellekaan NG, Young GP and James RJ: Reduced accumulation of specific miRNAs in colorectal neoplasia. Mol Cancer Res. 1:882–891. 2003.

8. 

Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T and Takahashi T: Reduced expression of the let-7 miRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 64:3753–3756. 2004. View Article : Google Scholar : PubMed/NCBI

9. 

Borel F, Konstantinova P and Jansen PL: Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma. J Hepatol. 56:1371–1383. 2012. View Article : Google Scholar : PubMed/NCBI

10. 

Kozaki KI and Inazawa J: Tumor-suppressive microRNA silenced by tumor-specific DNA hypermethylation in cancer cells. Cancer Sci. 103:837–845. 2012. View Article : Google Scholar : PubMed/NCBI

11. 

Zen K, Yasui K, Nakajima T, Zen Y, Zen K, Gen Y, Mitsuyoshi H, Minami M, Mitsufuji S, Tanaka S, Itoh Y, Nakanuma Y, Taniwaki M, Arii S, Okanoue T and Yoshikawa T: ERK5 is a target for gene amplification at 17p11 and promotes cell growth in hepatocellular carcinoma by regulating mitotic entry. Genes Chromosomes Cancer. 48:109–120. 2009. View Article : Google Scholar : PubMed/NCBI

12. 

Hatada I, Fukasawa M, Kimura M, Morita S, Yamada K, Yoshikawa T, Yamanaka S, Endo C, Sakurada A, Sato M, Kondo T, Horii A, Ushijima T and Sasaki H: Genome-wide profiling of promoter methylation in human. Oncogene. 25:3059–3064. 2006. View Article : Google Scholar : PubMed/NCBI

13. 

Hatada I, Morita S, Kimura M, Horii T, Yamashita R and Nakai K: Genome-wide demethylation during neural differentiation of P19 embryonal carcinoma cells. J Hum Genet. 53:185–191. 2008. View Article : Google Scholar : PubMed/NCBI

14. 

Hatada I, Namihira M, Morita S, Kimura M, Horii T and Nakashima K: Astrocyte-specific genes are generally demethylated in neural precursor cells prior to astrocytic differentiation. PLoS One. 3:e31892008. View Article : Google Scholar : PubMed/NCBI

15. 

Xiong Z and Laird PW: COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Res. 25:2532–2534. 1997. View Article : Google Scholar : PubMed/NCBI

16. 

Dohi O, Takada H, Wakabayashi N, Yasui K, Sakakura C, Mitsufuji S, Naito Y, Taniwaki M and Yoshikawa T: Epigenetic silencing of RELN in gastric cancer. Int J Oncol. 36:85–92. 2010.PubMed/NCBI

17. 

Rodriguez A, Griffiths-Jones S, Ashurst JL and Bradley A: Identification of mammalian microRNA host genes and transcription units. Genome Res. 14:1902–1910. 2004. View Article : Google Scholar : PubMed/NCBI

18. 

Kim YK and Kim VN: Processing of intronic microRNAs. EMBO J. 26:775–783. 2007. View Article : Google Scholar

19. 

Saini HK, Griffiths-Jones S and Enright AJ: Genomic analysis of human microRNA transcripts. Proc Natl Acad Sci USA. 104:17719–17724. 2007. View Article : Google Scholar : PubMed/NCBI

20. 

Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL and Massague J: Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 451:147–152. 2008. View Article : Google Scholar : PubMed/NCBI

21. 

Png KJ, Yoshida M, Zhang XH, Shu W, Lee H, Rimner A and Chan TA: MicroRNA-335 inhibits tumor reinitiation and is silenced through genetic and epigenetic mechanisms in human breast cancer. Genes Dev. 25:226–231. 2011. View Article : Google Scholar

22. 

Scarola M, Schoeftner S, Schneider C and Benetti R: miR-335 directly targets Rb1 (pRb/p105) in a proximal connection to p53-dependent stress response. Cancer Res. 70:6925–6933. 2010. View Article : Google Scholar : PubMed/NCBI

23. 

Tome M, Lopez-Romero P, Albo C, Sepulveda JC, Fernandez-Gutierrez B, Dopazo A, Bernad A and Gonzalez MA: miR-335 orchestrates cell proliferation, migration and differentiation in human mesenchymal stem cells. Cell Death Differ. 18:985–995. 2011. View Article : Google Scholar : PubMed/NCBI

24. 

Shu M, Zheng X, Wu S, Lu H, Leng T, Zhu W, Zhou Y, Ou Y, Lin X, Lin Y, Xu D, Zhou Y and Yan G: Targeting oncogenic miR-335 inhibits growth and invasion of malignant astrocytoma cells. Mol Cancer. 10:592011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Dohi O, Yasui K, Gen Y, Takada H, Endo M, Tsuji K, Konishi C, Yamada N, Mitsuyoshi H, Yagi N, Yagi N, et al: Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma. Int J Oncol 42: 411-418, 2013.
APA
Dohi, O., Yasui, K., Gen, Y., Takada, H., Endo, M., Tsuji, K. ... Yoshikawa, T. (2013). Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma. International Journal of Oncology, 42, 411-418. https://doi.org/10.3892/ijo.2012.1724
MLA
Dohi, O., Yasui, K., Gen, Y., Takada, H., Endo, M., Tsuji, K., Konishi, C., Yamada, N., Mitsuyoshi, H., Yagi, N., Naito, Y., Tanaka, S., Arii, S., Yoshikawa, T."Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma". International Journal of Oncology 42.2 (2013): 411-418.
Chicago
Dohi, O., Yasui, K., Gen, Y., Takada, H., Endo, M., Tsuji, K., Konishi, C., Yamada, N., Mitsuyoshi, H., Yagi, N., Naito, Y., Tanaka, S., Arii, S., Yoshikawa, T."Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma". International Journal of Oncology 42, no. 2 (2013): 411-418. https://doi.org/10.3892/ijo.2012.1724
Copy and paste a formatted citation
x
Spandidos Publications style
Dohi O, Yasui K, Gen Y, Takada H, Endo M, Tsuji K, Konishi C, Yamada N, Mitsuyoshi H, Yagi N, Yagi N, et al: Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma. Int J Oncol 42: 411-418, 2013.
APA
Dohi, O., Yasui, K., Gen, Y., Takada, H., Endo, M., Tsuji, K. ... Yoshikawa, T. (2013). Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma. International Journal of Oncology, 42, 411-418. https://doi.org/10.3892/ijo.2012.1724
MLA
Dohi, O., Yasui, K., Gen, Y., Takada, H., Endo, M., Tsuji, K., Konishi, C., Yamada, N., Mitsuyoshi, H., Yagi, N., Naito, Y., Tanaka, S., Arii, S., Yoshikawa, T."Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma". International Journal of Oncology 42.2 (2013): 411-418.
Chicago
Dohi, O., Yasui, K., Gen, Y., Takada, H., Endo, M., Tsuji, K., Konishi, C., Yamada, N., Mitsuyoshi, H., Yagi, N., Naito, Y., Tanaka, S., Arii, S., Yoshikawa, T."Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma". International Journal of Oncology 42, no. 2 (2013): 411-418. https://doi.org/10.3892/ijo.2012.1724
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