| Project/Area Number |
20K16407
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Gunma University |
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Principal Investigator |
Ishii Norihiro 群馬大学, 医学部附属病院, 助教 (00711508)
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 肝胆膵 / 膵癌 / 治療抵抗性 / 悪性 / RRN3 / 抗癌剤感受性 / リボソーム / 転写 / TIF-1A / 予後因子 / 増殖能 / 浸潤能 / 薬剤感受性 / リボソーム合成 / 予後不良 / 肝胆膵癌 / 癌関連線維芽細胞 / M2BPGi / リボソームRNA |
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| Outline of Research at the Start |
肝胆膵領域癌は予後不良であり、予後改善のためには悪性化機序の解明やそれらを標的とした新たな治療戦略が求められている。肝細胞癌、膵癌細胞の癌関連線維芽細胞より産生されるM2BPGiの癌促進効果の解析から新たに同定されたリボソームRNAの転写促進因子であるRRN3の肝胆膵癌の悪性化における意義を解明し、治療標的としての可能性について解析する。
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| Outline of Final Research Achievements |
Pancreatic cancer is an extremely poor prognosis. The RNA-polymerase I mediated transcription is essential initial step for ribosome biogenesis and are related with cancer cell malignancy. RRN3 is RNA polymerase I specific transcription initiation factor. We found that high level of RRN3 expression was associated with Ki-67 expression and shorter overall survival compared with RRN3 low expression. In addition, proliferation and invasion ability were decreased when RRN3 was silenced with siRNA compared to control siRNA transfected cells. Chemosensitivity analysis showed that inhibition of RRN3 enhanced sensitivity of anticancer drug. Furthermore, RRN3 siRNA-transfected PANC-1 tumors showed significantly reduced tumor volumes compared to the control tumors in a mouse xenograft model. High RRN3 expression associated with poor prognosis and cancer malignancy in pancreatic cancer. RRN3 targeting may be a promising therapeutic strategy to overcome refractory pancreatic cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
肝胆膵癌は難治性固形癌の代表であり、治療成績はまだ十分とは言えない。癌の悪性度に関わる分子の解析が進むことで、治療成績の向上に結び付く可能性がある。RRN3蛋白が膵癌の悪性度（増殖能や浸潤能、抗癌剤抵抗性）に関わることが示されたため、RRN3を軸とした治療戦略は、膵癌の治療抵抗性を克服する新たな治療法の一つとなる可能性がある。
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