| Project/Area Number |
16K10539
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Digestive surgery
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
|
|---|
| Research Collaborator |
Sakaguchi Masazumi 京都大学大学院医学研究科, 消化管外科, 大学院生
Shimono Yohei 藤田医科大学医学部, 生化学講座, 教授
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | 大腸癌 / マイクロRNA / 大腸癌幹細胞 / 正常大腸幹細胞 / DCLK1 / 外科 / 癌 |
|---|
| Outline of Final Research Achievements |
DCLK1-positive colon cancer cells were widely distributed in the colon cancer specimens, while DCLK1-positive epithelial cells were rarely detected in normal colon tissues, including the crypt bottoms. MiRNA-137(miR-137) was highly expressed in the NCoSC population, whereas the DCLK1 mRNA expression was significantly upregulated in the CoCSC population. The defect in organoid development by the transduction of miR-137 and shRNAs were substantially rescued by co-expression of the exogenous DCLK1. Although miRNA-137 overexpression did not affect the organoid development of the normal intestine, miRNA-137 knockdown promoted the organoid development of normal colon cells. miR-137 has the potential function to suppress the tumorigenicity of CoCSCs and that maintained expression of miR-137 in NCoSCs contributes to suppress uncontrolled cell proliferation through the inhibition of DCLK1 expression.
|
| Academic Significance and Societal Importance of the Research Achievements |
正常大腸幹細胞(NCoSCs)と大腸癌幹細胞(CoCSCs)は、組織再形成・細胞増殖のため共通のメカニズムを有していると考えられている。近年マウスを用いた研究で、DCLK1が、正常大腸には発現せず、小腸腺腫の幹細胞にのみ発現していることが報告されたが、ヒトCoCSCsとDCLK1の発現については詳細な研究は進んでいなかった。
今回の我々の研究結果から、miR-137はDCLK1発現を制御することでCoCSCsの腫瘍形成能を抑制することが示唆された。本結果から正常大腸組織を障害せずCoCSCsを標的とした新規治療戦略を提示できる可能性があると考える。
|
