2020 Fiscal Year Final Research Report
Mechanisms underlying gene expression mediated by 3'UTR of cancer-related gene
Project/Area Number |
19K22576
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 50:Oncology and related fields
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Research Institution | Aichi Cancer Center Research Institute |
Principal Investigator |
Oneyama Chitose 愛知県がんセンター(研究所), 腫瘍制御学分野, 分野長 (90373208)
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Project Period (FY) |
2019-06-28 – 2021-03-31
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Keywords | がん関連遺伝子 / 3'UTR / 発現制御機構 / Rictor / 化合物 |
Outline of Final Research Achievements |
The aim of this study is to elucidate a new mechanism of expression regulation via the 3'UTR of cancer-related genes. Through our previous studies, we found a small molecule compound that suppresses the expression of Rictor gene, which is important for the survival and motility of cancer cells, via the 3'UTR. In order to identify candidate target proteins of the compounds, we identified three proteins known to be involved in the regulation of splicing, transcription, and translation by using the originally developed "target identification method using changes in protease sensitivity" in addition to the molecular probe method. We identified three proteins known to be involved in splicing, transcription, and translation regulation. Detailed analysis revealed that one RNA-binding protein was the target protein of the compound.
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Free Research Field |
腫瘍学
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Academic Significance and Societal Importance of the Research Achievements |
本研究内容にあるmiRNAの作用を低分子化合物により代替するというアイデアは極めて斬新なものである。元来miRNAは遺伝子の主に3'UTRを介し核酸配列の相補性に基づいて作用するため、核酸医薬を用いずに低分子を用いて代替できるとは考えられていなかった。しかし、私は3’UTRを標的とするスクリーニングに挑戦し、Rictor遺伝子の発現調節過程を低分子化合物によって制御することに成功した。本研究によってその分子基盤解明に挑戦することは、特定の遺伝子発現を3’UTRを介して制御する新しい原理の発見につながる点で、これまでの遺伝子発現制御機構の研究及び対がん創薬研究を大きく変革させる潜在性を有する。
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