Induction of cellular senescence by HOXB9 for tailor-made treatment

Research Project

Project/Area Number	15K10072
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	General surgery
Research Institution	Tokyo Medical University
Principal Investigator	Chiba Naokazu 東京医科大学, 医学部, 講師 (90348665)
Project Period (FY)	2015-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	HOXB9 / Cellular Senescence / HoxB9 / Cellular Senesence / p21 / Cellular Senecense / Cellular Scenesence / p21/p53
Outline of Final Research Achievements	Positive cells in b-Galactosidase and PML were up-regulated and p21 genes and G1 phase cells were amplified by induction of HOXB9. On the other hand, knocking down of p21 and HOXB9 also attenuated cellular senescence. The results showed that HOXB9 induces cellular senescence via p21 pathway. In addition, in the surgically resected specimens, HOXB9 and p21 were positively correlated, suggesting that HOXB9 and p21 are related.
Academic Significance and Societal Importance of the Research Achievements	Cellular Senescenceのメカニズムに関する報告は散見されるが、臨床応用に至っているものは少なく、既に乳癌や肝細胞癌の予後因子として研究が進められているHOXB9と、これによるCellular Senescenceのメカニズム解明を意図した研究は未だかつてない。老化関連遺伝子、癌遺伝子、癌抑制遺伝子は幹細胞機能維持、細胞老化（Cellular Senescence）、細胞癌化という生物現象にそれぞれオーバーラップしながら関わっていると考えられ、以上の一連の研究成果から、HOXB9が癌治療の個別化バイオマーカーとなり、最終的には新たな分子標的治療薬の開発の一端を担う可能性がある。