2022 Fiscal Year Final Research Report
Molecular mechanism of accumulation of cytoplasmic chromatin in senescent cells, related to carcinogenesis
Project/Area Number |
20K07589
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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 |
Review Section |
Basic Section 50010:Tumor biology-related
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Research Institution | Kumamoto University |
Principal Investigator |
Watanabe Sugiko 熊本大学, 発生医学研究所, 特定事業研究員 (10433012)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | がん / 細胞老化 / ゲノム不安定性 / 全ゲノム解析 |
Outline of Final Research Achievements |
Persistent cellular stresses induce senescence, in which accumulation of cytoplasmic chromatin fractions (CCFs) is observed. The purpose of this study is to clarify the relationship between senescence and genome instability leading to carcinogenesis by next-generation sequence (NGS) of CCFs. Analysis revealed that the DNA sequences found in the cytoplasmic fraction of senescent cells show a specific clustering that is clearly different from that of DNA present in the nucleus and cytoplasm of healthy cells. Furthermore, some genomic regions specifically increasing in the cytoplasm of senescent cells exhibit structural variants in clinical cancer tissues. These data suggests that cellular senescence is associated with genomic instability leading to carcinogenesis. Based on this data, further applied research is expected in the future.
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Free Research Field |
がん
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Academic Significance and Societal Importance of the Research Achievements |
細胞老化の誘導に伴って細胞質に増加するDNA配列を解析し、実際のがん組織で認められているゲノム不安定性との関連を見出した。細胞老化を起こした細胞は加齢により体内に蓄積することが知られており、加齢性発がんとの関連が示唆されているが、その分子メカニズムは不明である。本研究成果は、加齢に伴って増加する発がんの分子メカニズムの一端を細胞質のゲノム解析から明らかにするものである。加齢性発がんの理解を深めることに加え、今後の応用解析によって、発がんやがん治療効果のモニター、さらには新たな治療戦略創出に役立つであろうことが期待できる。
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