2007 Fiscal Year Final Research Report Summary
Exploration of oncogenic or tumor-suppressive microRNAs in oral cancer.
| Project/Area Number |
18591997
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
KOZAKI Ken-ichi Tokyo Medical and Dental University, Medical Research InstituteGraduate School,, Associate Professor (50270715)
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| Co-Investigator(Kenkyū-buntansha) |
INAZAWA Johji Tokyo Medical and Dental University, Medical Research Institute, Graduate School, Professor (30193551)
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| Project Period (FY) |
2006 – 2007
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| Keywords | oral cancer / squamous cell carcinoma / microRNA / miR-137 / miR-193a / oncogene / tumor suppressor gene |
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| 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.
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[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.
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Journal Title
Oncogene 26
Pages: 7921-7932
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Oncogene 26
Pages: 6456-6468
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Cancer Sci 98
Pages: 1078-1086
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Cancer Sri 98
Pages: 1070-1077
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Cancer Sri 97
Pages: 1351-1358
Description
「研究成果報告書概要(欧文)」より
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