2016 Fiscal Year Final Research Report
Functional analysis of large intergenic non-coding RNAs regulated by p53 in cancers of digestive organs
Project/Area Number |
25460929
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Sapporo Medical University |
Principal Investigator |
|
Project Period (FY) |
2013-04-01 – 2017-03-31
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Keywords | p53 / lncRNA / ChIP-seq / 癌 / lincRNA / non-coding RNA |
Outline of Final Research Achievements |
p53 is one of the most important known tumor suppressor genes, and it is inactivated in approximately half of human cancers. To identify the direct transcriptional targets of p53, we performed chromatin immunoprecipitation together with next-generation sequencing (ChIP-seq) and searched for p53 binding motifs across the entire human genome. Among the identified ChIP-seq peaks, approximately half were located in an intergenic region. Therefore, we assumed large intergenic non-coding RNAs (lincRNAs) to be major targets of the p53 family. Through a combination of ChIP-seq and in silico analyses, we found 23 lincRNAs that are upregulated by the p53 family. Additionally, knockdown of specific lincRNAs modulated p53-induced apoptosis and promoted the transcription of a gene cluster. Our results suggest that p53 family members and lincRNAs constitute a complex transcriptional network involved in various biological functions and tumor suppression.
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Free Research Field |
腫瘍学,消化器内科学
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