2011 Fiscal Year Final Research Report
Prediction of drug sensitivity and development of a therapeutic strategy by microRNAs in lung cancer
| Project/Area Number |
21591008
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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 |
Respiratory organ internal medicine
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
GEMMA Akihiko 日本医科大学, 大学院・医学研究科, 教授 (20234651)
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| Co-Investigator(Renkei-kenkyūsha) |
MINEGISHI Yuji 日本医科大学, 医学部, 講師 (80386234)
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| Project Period (FY) |
2009 – 2011
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| Keywords | マイクロRNA / 肺癌 / 薬剤感受性 |
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| Research Abstract |
We tried to identify microRNAs(miRNAs) associated with drug sensitivity of lung cancer and establish a new therapeutic strategy in lung cancer. First, we analyzed miRNA expression profiles of 30 lung cancer cell lines using Taqman MicroRNA Arrays. Four miRNAs(miR-21, miR-31, miR-193b and miR-365) were common miRNAs correlated with the sensitivity of lung cancer to nine anticancer drugs. Next, we analyzed the antitumor effects of enzastaurin in 22 lung cancer cell lines. To identify miRNA associated with this sensitivity, we conducted a miRNA expression profiling study on the same set of cell lines. We found that miR-21 affects the response to enzastaurin through the JAK/STAT signaling pathway in lung cancer. Finally, we analyzed miR-23a/24/27a expression in 10 non-small cell cancer cell lines by real-time PCR analysis. Correlation between expression of these miRNAs and epithelial-mesenchymal transition(EMT) was evaluated. We found that miR-23a regulated TGF-β-induced EMT by targeting E-cadherin and contributed to EGFR-TKI resistance of lung cancer cells. These miRNAs associated with drug sensitivity may be useful as new therapeutic targets in lung cancer.
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Research Products
(14 results)
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[Journal Article] Enzastaurin has anti-tumour effects in lung cancers with overexpressed JAK pathway molecules2012
Author(s)
Shimokawa T, Seike M, Soeno C, Uesaka H, Miyanaga A, Mizutani H, Kitamura K, Minegishi Y, Noro R, Okano T, Yoshimura A, Gemma A
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Journal Title
Br J Cancer
Volume: 106
Pages: 867-875
DOI
Peer Reviewed
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[Journal Article] HSP27 modulates epithelial to mesenchymal transition of lung cancer cells in a Smad-independent manner2010
Author(s)
Mizutani H, Okano T, Minegishi Y, Matsuda K, Sudoh J, Kitamura K, Noro R, Soeno C, Yoshimura A, Seike M, Gemma A
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Journal Title
Oncology Letter
Volume: 1
Pages: 1011-1016
DOI
Peer Reviewed
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