| Project/Area Number |
15K09500
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kagawa University (2017-2018)
Kyoto University (2015-2016) |
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Principal Investigator |
|
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| Research Collaborator |
Kadowaki Norimitsu
Kawahara Masahiro
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| Project Period (FY) |
2015-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | DHX29 / DDX41 / 造血器腫瘍 / 細胞内核酸センサー / eIF4E / eIF4GI / eIF4F / 細胞質内核酸センサー / 血液細胞 / 核酸センシング / 自然免疫 / 造腫瘍性 |
|---|
| Outline of Final Research Achievements |
The expression of DHX29 was not observed in fresh peripheral blood subsets, but induced in differentiated monocytes and activated T, B and NK cells. DHX29 was highly expressed in all 10 of various hematopoietic cell lines and in 4 out 6 blood samples of patients with hematological malignancies. Knockdown of DHX29 showed no apparent effect in cell proliferation and immune responses, but 4EGI-1, an inhibitor of eIF4E/eIF4F which cooperate with DHX29, significantly suppressed the proliferation and downregulated the expression of c-MYC. These results suggest that DHX29 contributes to tumorigenesis of hematological malignancies through cooperation with other translation relates proteins to endow tumor growth advantage.
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| Academic Significance and Societal Importance of the Research Achievements |
DExD/Hヘリカーゼ・ファミリー分子に属するDHX29やDDX41は、mRNAの翻訳や腫瘍細胞の生存・ 増殖、細胞質内のウィルス・核酸センサーとして働いている。DDX41は急性骨髄性白血病の病態発生に関与し、DHX29もeIF4E/eIF4Fと協調して癌細胞で働いていると報告されているが、今回の研究によりDHX29およびeIF4E/eIF4Fは造血器腫瘍の病態にも関与していることが示唆される結果が得られ、今後造血器悪性疾患の新たな治療標的となると見込まれる。
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