| Project/Area Number |
18K15248
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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 50010:Tumor biology-related
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| Research Institution | University of Miyazaki (2020-2021)
Kagoshima University (2018-2019) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 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 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 遺伝子増幅 / 抗癌剤耐性 / 抗がん剤耐性 / 遺伝子増幅の減少 / タンパク質分解 / 増殖抑制 / 肺癌 / 腫瘍抑制因子 |
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| Outline of Final Research Achievements |
Gene amplification is thought to be related to the breakage-fusion-bridge cycle, but the mechanism of development and maintenance are unclear.The purpose of this study was to analyze the mechanism of reduction of gene amplification by BHLHE41.When BHLHE41 is expressed, it takes 21 days for the amplified gene to decrease, and RNAseq analysis was performed to examine the genes changed during this period. In comparison between the day 0 and the day 2 of DOX treatment, where the gene for gene repair and replication had already changed on the day 2. Furthermore, the expression of these genes was higher on the day 28 than on the day 2. These results suggest that changes in these genes over a long period of time reduce gene amplification.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでに遺伝子増幅を持つ細胞にBHLHE41が発現すると遺伝子増幅が減少することを明らかにしている。
BHLHE41の発現初期から遺伝子増幅が減少する間に遺伝子修復や複製に関わる遺伝子が変化していたことから長期的にそれら遺伝子が変化し続けることで遺伝子増幅が減少することが示唆された。BHLHE41の発現制御メカニズムもメチル化やタンパク質分解が関わっていることを明らかした。遺伝子増幅の減少メカニズムやBHLHE41の制御分子がわかれば癌治療だけでなく他の疾患にも応用ができることが考えられる。
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