| Project/Area Number |
16K15256
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | RNA修飾 / 肺がん / m6A / WTAP / METTL3 / METTL14 / FTO / ALKBH5 / ヒトがん / 6 methyl adenine / YTHFD1 / YTHFD2 / DNA付加体 / RNA付加体 / RNA塩基修飾酵素 / アダクトミクス |
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| Outline of Final Research Achievements |
m6A measurement in human cancer tissue revealed m6A is relatively abundant in tumor portion of the lung and high m6A/A was related to the worse prognosis of the lung cancer. To elucidate the biological basis of this observation, modifying enzymes METTL14, METTL3, WTAP, FTO, ALKBH5, YTHDF1, YTHDF2 expression were investigated in 8 lung cancer cell lines and immortalized bronchial epithelium. Among them, WTAP, which is not expressed in immortalized bronchial epithelium and over expressed in lung cancer cell lines was investigated on its effect of siRNA and enforced overexpresssion. SiRNA experiment showed growth inhibition and decrease of m6A/A whereas over expression induced growth promotion. Immunoprecipitation analysis confirm its modification on EGFR 3UTR mA. Finally using our clinical cohort of 642 lung cancer cases, expression of WTAP in human lung cancer tissues are related to the prognosis including performance status and overall survival.
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