| Project/Area Number |
18K08669
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 55020:Digestive surgery-related
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
内藤 剛 東北大学, 医学系研究科, 准教授 (50291258)
大沼 忍 東北大学, 大学病院, 助教 (70451565)
中山 啓子 東北大学, 医学系研究科, 教授 (60294972)
舟山 亮 東北大学, 医学系研究科, 助教 (20452295)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
|---|
| Keywords | 大腸癌 / マイクロエクソン |
|---|
| Outline of Final Research Achievements |
Microexons are very small exons, whose alternative splicing is frequently deregulated in a neurological disease, autism spectrum disorder. However, little is known about the splicing pattern, regulatory mechanisms, and roles of microexon in cancer. We have examined the transcriptome-wide profile of microexon splicing in matched normal colon and colorectal cancer (CRC) tissue specimens. Out of 1,492 microexons with shorter than 15 nucleotides in length, seventeen (1%) were differentially spliced between normal colon and CRC tissues. Analyses of RNA sequence motifs, an RNA-binding protein database, and subsequent shRNA-mediated knockdown identified two splicing factors, RBFOX2 and PTBP1, as regulators of microexon splicing. Our data thus suggest that the altered expression of RBFOX2 and PTBP1 might affect cell adhesion and migration of CRC cells through the regulation of microexon splicing.
|
| Academic Significance and Societal Importance of the Research Achievements |
癌におけるマイクロエクソンのスプライシングパターンの変化や、スプライシング異常が癌の進行に果たす役割はほとんど研究されていなかったが、本研究により、マイクロエクソンのスプライシング制御機構の破綻は、タンパク質-タンパク質間相互作用を変化させ、大腸癌細胞の接着能、遊走能、および転移能に影響しうることが示唆され、マイクロエクソンのスプライシング変化の臨床的意義について新知見が得られた。
|
