2019 Fiscal Year Final Research Report
The analysis of non-coding RNA induced by cancer-associtated transcriptional factors in gastrointestinal cancers
| Project/Area Number |
16K09285
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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 |
Gastroenterology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | 癌 / 非コードRNA / p53 / NEAT1 / lncRNA / non-coding RNA |
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| Outline of Final Research Achievements |
p53 is one of the most important tumor suppressor genes and the direct transcriptional targets of p53 must be explored to elucidate its functional mechanisms. Thus far, the p53 targets that have been primarily studied are protein-coding genes. In this study, analysis of next-generation chromatin immunoprecipitation-sequencing (ChIP-seq) data for p53 revealed that the lncRNA NEAT1 is a direct transcriptional target of p53. The suppression of NEAT1 induction by p53 attenuates the inhibitory effect of p53 on cancer cell growth and also modulates gene transactivation, including that of many lncRNAs. Furthermore, low expression of NEAT1 is related to poor prognosis in several cancers. These results indicate that the induction of NEAT1 expression contributes to the tumor-suppressor function of p53 and suggest that p53 and NEAT1 constitute a transcriptional network contributing to various biological functions and tumor suppression.
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| Free Research Field |
腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
癌は死因の第一位であり新たな診断治療法の開発が急務である．これまでの研究は蛋白を中心に行われてきたが，近年，蛋白にならない非コードRNAが重要な役割を果たしていることが分かってきた．本研究では癌で最も高頻度に変異している癌抑制遺伝子p53の標的となる非コードRNAを新たに見出した．これによりp53による発癌の抑制機構の一端が明らかになると共に，新たな癌の診断治療への端緒となる可能性も秘めている．
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