Elucidation of transformation mechanism from benign tumor to cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H04700
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Takahashi Akiko 公益財団法人がん研究会, がん研究所 細胞老化プロジェクト, プロジェクトリーダー (60380052)
• Research Collaborator: MIYATA kenichi ; OKADA ryo
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 細胞老化 / エピジェネティクス / non-coding RNA / 染色体不安定性

Outline of Final Research Achievements

Cellular senescence is the state of essentially irreversible cell cycle arrest that can be induced by a variety of potentially oncogenic stimuli and is therefore considered to act as an important tumor suppression mechanism in vivo. On the other hand, cellular senescence also causes secretion of various inflammatory factors, which seems to contribute age-associated diseases. We have investigated that epigenetic de-regulation of genomic DNA induces the aberrant expression of non-coding RNA in senescent cells. Surprisingly, ectopic expression of non-coding RNA provokes chromosomal instability, which resulted in tumorigenesis in mice. It is therefore possible that the overexpression of non-coding RNA in old mice may eventually promotes tumorigenesis, especially in case of accidental re-initiation of cell proliferation in senescent cells. These results indicate that senescence-associated epigenetic dysregulation may contribute to transformation from benign tumor to cancer.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、老化した細胞では染色体のヘテロクロマチン領域のH3K9me3のレベルが低下し若い細胞では発現していないnon-coding RNAが産生されており、このnon-coding RNAは正常な細胞に染色体分配の異常を引き起こし腫瘍形成能を獲得させることを明らかにした。つまり、加齢に伴って体内に蓄積した老化細胞で高発現するnon-coding RNAが、染色体不安定性を誘導し腫瘍細胞へと形質転換をおこさせる可能性が示唆された。今後は細胞老化特異的なnon-coding RNAを標的とした新しい診断法や治療法の開発が期待される。