| Project/Area Number |
18K15631
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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 52040:Radiological sciences-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 放射線治療抵抗性 / エピジェネティクス / エピトランスクリプトーム / METTL3 / RNAメチル化 / alternative splicing / 放射線抵抗性 / エピジェネティック / CTCF / DNA高次構造 |
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| Outline of Final Research Achievements |
The purpose of this study is to elucidate a broadly defined epigenetic mechanism related to resistance to radiotherapy. We showed increased expression of METTL3, an RNA methylase, was related with the resistance for radiation therapy and PLK1 was an important role as its target gene in pancreatic cancer cell lines. Furthermore, we found that there was a correlation between METTL3 and PLK1 expression, and that PLK1 inhibitors increased radiosensitivity regardless of METTL3 expression level. We are also analyzing the effects of their expression on therapeutic sensitivity in patients with pancreatic cancer treated with preoperative chemoradiotherapy, as well as PLK1 expression changes due to site-specific methylation inhibition using dCAS9.
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| Academic Significance and Societal Importance of the Research Achievements |
当初の研究課題であったDNA高次構造の変化による放射線治療抵抗性への関与の解析の前に、同じく広義のエピジェネティックな機序であるRNAメチル化の関与を解析した形となったが、集学的治療などの医学が発展した現代においても様々な治療に対して抵抗性であり難治性である膵癌において、新たな治療標的を発見することができた。PLK1阻害剤に関しては海外で主に血液悪性疾患に対しての治療として治験が進められているが、今回の研究成果からは膵癌に対して放射線治療とPLK1阻害剤の併用の可能性に希望を持てる結果であった。
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