2019 Fiscal Year Final Research Report
A comprehensive search for miRNAs regulated by histone deacetylase in malignant lymphoma
| Project/Area Number |
17K16178
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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 |
Hematology
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| Research Institution | Akita University (2019)
Kameda College of Health Sciences (2017-2018) |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 悪性リンパ腫 / T細胞リンパ腫 / HDAC / HDAC阻害剤 / CCR4 |
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| Outline of Final Research Achievements |
We found that HDAC inhibitors restore expression of many tumor suppressive microRNAs. In particular, it was revealed that restoration of miR-150 expression caused a decrease in the expression of chemokine receptor CCR6. Moreover, we found that the expression of another chemokine receptor, CCR4, is also decreased. Importantly, in vitro studies revealed that the efficacy of the anti-CCR4 antibody mogamulizumab may be diminished by pre-treatment of HDAC inhibitors. These findings may have important implications for the establishment therapeutic strategies for T-cell lymphoma.
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| Free Research Field |
血液内科
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| Academic Significance and Societal Importance of the Research Achievements |
HDAC阻害剤はT細胞リンパ腫における新規治療薬として登場したが、その作用機序は十分明らかではなかった。今回HDAC阻害剤ががん抑制的microRNAの発現を回復させ、ケモカインレセプターの発現を低下させることを見出した。特に重要な点として、ケモカインレセプターCCR4の発現を低下させることが挙げられる。CCR4はT細胞リンパ腫における別の新規治療薬であるモガムリズマブの標的抗原である。これにより、HDAC阻害剤とモガムリズマブの併用が有用でないことが示唆され、T細胞リンパ腫の最適な治療戦略確立に重要な示唆をもたらすものと思われる。
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