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Exploration of oncogenic or tumor-suppressive microRNAs in oral cancer.

Research Project

Project/Area Number 18591997
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

KOZAKI Ken-ichi  Tokyo Medical and Dental University, Medical Research InstituteGraduate School,, Associate Professor (50270715)

Co-Investigator(Kenkyū-buntansha) INAZAWA Johji  Tokyo Medical and Dental University, Medical Research Institute, Graduate School, Professor (30193551)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsoral cancer / squamous cell carcinoma / microRNA / miR-137 / miR-193a / oncogene / tumor suppressor gene / 扁平上皮 / 網羅的ゲノム解析 / 網羅的発現解析
Research Abstract

In the last few years, microRNAs (miRNAs) have started a revolution in molecular biology and emerged as key players in the carcinogenesis. They have been identified in various tumor types, showing that different sets of miRNAs are usually deregulated in different cancers. To identify the miRNA signature that was specific for oral squamous cell carcinoma (OSCC), we first examined expression profiles of 148 miRNAs in a panel of 18 OSCC cell lines and the immortalized oral keratinocyte line RT7 as a control. As compared with RT7, the expression of 54 miRNAs(36.5%) was frequently down-regulated in OSCC lines(< 0.5-fold expression, 〓 66.7% of 18 lines). Among these 54 miRNAs, we further analyzed four of these miRNAs. i.e., miR-34b, miR-137, miR-193a, and miR-203, located around CpG islands, to identify tumor-suppressive miRNAs silenced through aberrant DNA methylation. The expression of those four genes was restored by treatment with 5-aza-2'-deoxycytidine in OSCC cells lacking their expression. In addition, expression levels of the four miRNAs were inversely correlated with their DNA methylation status in the OSCC lines. In primary tumors of OSCC with paired normal oral mucosa, down-regulation of miRNA expression through tumor-specific hypermethylation was more frequently observed for miR-137 and miR-193a than for miR-34b and miR 203. Moreover, the ectopic transfection of miR-137 or miR-193a into OSCC lines lacking their expressions significantly reduced cell growth, with down-regulation of the translation of CDK6 or E2F6, respectively. Taken together, our results clearly demonstrate that miR-137 and miR-193a are tumor-suppressor miRNAs epigenetically silenced during oral carcinogenesis.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (24 results)

All 2008 2007 2006 Other

All Journal Article (21 results) (of which Peer Reviewed: 9 results) Presentation (2 results) Remarks (1 results)

  • [Journal Article] Exploration of tumor-suppressive micro RNAs silenced by DNA hypermethylation in oral cancer.2008

    • Author(s)
      Kozaki, K., et. al.
    • Journal Title

      Cancer Res. 68

      Pages: 2094-2105

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer2008

    • Author(s)
      Kozaki, K. Imoto, I., Mogi, S., Omura. K., and Inazawa, J.
    • Journal Title

      Cancer Res 68

      Pages: 2094-2105

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer.2008

    • Author(s)
      Kozaki, K., et. al.
    • Journal Title

      Cancer Res. 68

      Pages: 2094-2105

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PRTFDCl, a possible tumor-suppressor gene, is frequently silenced in oral squamous-cell carcinomas by aberrant promoter hypermethylation.2007

    • Author(s)
      Suzuki, E., et. al.
    • Journal Title

      Oncogene 26

      Pages: 7921-7932

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Frequent methylation-associated silencing of a candidate tumor-suppresser, CRABPl, in esophageal squamous-cell carcinoma.2007

    • Author(s)
      Tanaka, K., et. al.
    • Journal Title

      Oncogene 26

      Pages: 6456-6468

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Association of KLK5-overexpression with invasiveness of urinary bladder carcinoma cells.2007

    • Author(s)
      Shinoda, Y., et. al.
    • Journal Title

      Cancer Sci. 98

      Pages: 1078-1086

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] BCL2L2 is a probable target for novel 14q11.2 amplification detected in a non-small cell lung cancer cell line.2007

    • Author(s)
      Kawasaki, T., et. al.
    • Journal Title

      Cancer Sci. 98

      Pages: 1070-1077

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] PRTFDCI, a possible tumor-suppressor gene, is frequently silenced in oral squamous-cell carcinomas by aberrant promoter hypermethylation2007

    • Author(s)
      Suzuki, E., Imoto, I., Pinikhaokham, A., Nakagawa, T., Kamata. N., Kozaki, K., Amagasa, T., and Inazawa, J.
    • Journal Title

      Oncogene 26

      Pages: 7921-7932

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Frequent methylation-associated silencing of a candidate tumor-suppressor, CRABP1, in esophageal squamous-cell carcinoma2007

    • Author(s)
      Tanaka, K., Imoto, I., Inoue. J., Kozaki K., Tsuda, H., Shimada. Y., Aiko, S., Yoshizumi, Y. Iwai. T., Kawano. T. and Inazawa. J.
    • Journal Title

      Oncogene 26

      Pages: 6456-6468

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Association of KLK5-overexpression with invasiveness of urinary bladder carcinoma cells2007

    • Author(s)
      Shinoda. Y., Kozaki, K., Imoto, I., Obara. W., Tsuda,H., Mizutani, Y., Shuin, T., Fujioka, T., Miki, T., and Inazawa, J.
    • Journal Title

      Cancer Sci 98

      Pages: 1078-1086

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] BCL2L2 is a probable target for novel 14q11.2 amplification detected in a non-small cell lung cancer cell line2007

    • Author(s)
      Kawasaki, T., Yokoi, S., Tsuda, H., Izumi, H., Kozaki K., Aida, S., Ozeki. Y., Yoshizawa, Y. Imoto, I. and Inazawa, J.
    • Journal Title

      Cancer Sri 98

      Pages: 1070-1077

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] PRTFDCI, a possible tumor-suppressor gene, is frequently silenced in oral squamous-cell carcinomas by aberrant promoter hypermethylation.2007

    • Author(s)
      Suzuki, E., et. al.
    • Journal Title

      Oncogene 26

      Pages: 7921-7932

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequent methylation-associated silencing of a candidate tumor-suppressor, CRABPI, in esophageal squamous-cell carcinoma.2007

    • Author(s)
      Tanaka, K., et. al.
    • Journal Title

      Oncogene 26

      Pages: 6456-6468

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RGC32, a novel p53-inducible gene, is located on centrosomes during mitosis and results in G2/M arrest2007

    • Author(s)
      Saigusa, K., et al.
    • Journal Title

      Oncogene 26

      Pages: 1110-1121

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A novel amplification target, DUSP26, promotes anaplastic thyroid cancer cell growth by inhibiting p38 MAPK activity2007

    • Author(s)
      Yu, W., et al.
    • Journal Title

      Oncogene 26

      Pages: 1178-1187

    • Related Report
      2006 Annual Research Report
  • [Journal Article] PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma.2006

    • Author(s)
      Kozaki, K., et. al.
    • Journal Title

      Cancer Sci. 27

      Pages: 1351-1358

    • NAID

      10020387899

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] PIT3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma2006

    • Author(s)
      Kozaki. K., Imoto, I., Pimkhaokham, A., Hasegawa, S., Tsuda, H., Omura, K. and Inazawa, J.
    • Journal Title

      Cancer Sri 97

      Pages: 1351-1358

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma2006

    • Author(s)
      Kozaki, K., et al.
    • Journal Title

      Cancer Sci. 97

      Pages: 1351-1358

    • NAID

      10020387899

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genetic or epigenetic silencing of low density lipoprotein receptor-related protein 1B expression in oral squamous cell carcinoma2006

    • Author(s)
      Nakagawa, T., et al.
    • Journal Title

      Cancer Sci. 97

      Pages: 1070-1074

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genomic loss and epigenetic silencing of very-low-density lipoprotein receptor involved in gastric carcinogenesis2006

    • Author(s)
      Takada, H., et al.
    • Journal Title

      Oncogene 25

      Pages: 6554-6562

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Frequent silencing of the candidate tumor suppressor PCDH20 by epigenetic mechanism in non-small-cell lung cancers2006

    • Author(s)
      Imoto, I., et al.
    • Journal Title

      Cancer Res. 66

      Pages: 4617-4626

    • Related Report
      2006 Annual Research Report
  • [Presentation] Micro RNA expression profiles in oral squamous cell carcinoma cell lines.2007

    • Author(s)
      Kozaki, K., et. al.
    • Organizer
      American Association for Cancer Research, Annual Meeting 2007
    • Place of Presentation
      Los Angeles, CA
    • Year and Date
      2007-04-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] MicroRNA expression profiles in oral squamous cell carcinoma cell lines.2007

    • Author(s)
      Kozaki, K., et. al.
    • Organizer
      American Association for Cancer Research, Annual Meeting 2007
    • Place of Presentation
      Los Angeles, CA, USA
    • Year and Date
      2007-04-17
    • Related Report
      2007 Annual Research Report
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.tmd.ac.jp/mri/cgen/framepage.htm

    • Related Report
      2007 Final Research Report Summary

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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