Elucidation of expression mechanism to regulate repetitive RNA which acceralates pancreatic carcinogenesis
| Project/Area Number |
17K15923
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 反復配列RNA / 膵癌 / マウスモデル / 反復配列ＲＮＡ / トランスジェニックマウス / 消化器内科 |
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| Outline of Final Research Achievements |
Repetitive sequences are widely and abundantly spread through the genome with huge varieties. They were considered to be epigenetically silenced in physiological setting, among which, however, some subsets are reported to be aberrantly expressed in pancreatic cancer and pre-cancer lesions. In order to elucidate the molecular function of the repetitive RNAs in oncogenesis, we developed transgenic mice model that express repetitive RNA in whole body. We found that DNA damage repair function was suppressed and DNA mutation rate was increased in the pancreas in repetitive RNA expressing mice. And also repetitive RNA expression increases tumor formation in the pancreas in KRAS mutant mouse model. These results suggest that repetitive RNA functions as an intrinsic mutagen in the process of pancreatic cancer development.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、タンパク質をコードせず従来機能を持たないとされていた反復配列領域からの転写産物が、発癌早期から異常発現していること、さらにこの発現が発癌過程に伴う単なる副産物としてではなく、遺伝子変異原としての機能を有していることをマウスモデルを用いて証明した。これらの結果は発癌プロセスの進行にコーディング遺伝子の変異だけでなく、ノンコーディングRNAの発現変化も重要な役割を果たしていることを示唆しており、発癌メカニズムの解明に新しい側面からの解釈を加える一助となると考える。
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Report
(3 results)
Research Products
(10 results)
