Carcinogenesis related to inappropriate expression of microRNAs in digestive organ tumor
Project/Area Number |
21791312
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Single-year Grants |
Research Field |
Digestive surgery
|
Research Institution | Osaka Medical College |
Principal Investigator |
TAKAGI Takeshi Osaka Medical College, 医学部, 非常勤医師 (80531897)
|
Project Period (FY) |
2009 – 2010
|
Project Status |
Completed (Fiscal Year 2010)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
Keywords | 胃十二指腸外科学 / microRNA / 胃癌 / 大腸癌 / 5-FU耐性 / gastric cancer |
Research Abstract |
Down-regulation of specific microRNAs (miRNAs) occurs in human tumors, which suggests a function for miRNAs in tumor suppression. Here, we show that the expression levels of miRNAs (miRs)-143, -145 and -34a were decreased in most of human gastric cancers. The transfection experiments of human gastric NUGC-3 cells with miR-145 exhibited a greater growth inhibitory effect than that with miR-143. In NUGC-3 cells, the supra-additive effect on growth inhibition was shown by the combination treatment which are the exposure of 5-FU and transfection with miRs-143, -145, or 34a. Taken together, these findings suggest that miRs-143, -145 and 34a play as anti-oncomirs common to gastrointestinal tumors. On the other hand, miR-34a was one of the down-regulated microRNAs in human colon cancer DLD-1 cells. After the exposure at 30 mM of 5-FU, which enhanced PI3K/Akt signaling markedly in 5-FU resistant cells in comparison with original cells, the expression level of miR-34a was considerably down-regulated. Sirt1, which was one of the target genes for miR-34a and related to drug resistance, was strikingly up-regulated in 5-FU resistant cells. The enforced expression of miR-34a in 5-FU resistant cells enhanced sensitivity to 5-FU through down-regulation of Sirt1. The silencing Sirt1 by using siRNA for Sirt1 canceled the resistance to 5-FU in 5-FU resistant cells. These findings suggested that miR-34a regulates at least in part the sensitivity to 5-FU in human colon cancer DLD-1 cells.
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Report
(3 results)
Research Products
(5 results)