MicroRNA-197 influences 5-fluorouracil resistance via thymidylate synthase in colorectal cancer

被引:36
作者
Sun, Z. [1 ,2 ]
Zhou, N. [1 ,2 ]
Han, Q. [3 ]
Zhao, L. [1 ,2 ]
Bai, C. [1 ,2 ]
Chen, Y. [2 ,4 ]
Zhou, J. [1 ,2 ]
Zhao, R. C. [3 ,5 ]
机构
[1] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Oncol, Beijing 100730, Peoples R China
[2] Peking Union Med Coll, Beijing 100021, Peoples R China
[3] Chinese Acad Med Sci, Inst Basic Med Sci, Sch Basic Med, Peking Union Med Coll, Beijing 100730, Peoples R China
[4] Chinese Acad Med Sci, Dept Digest, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China
[5] Peking Union Med Coll Hosp, Ctr Translat Med, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-197; 5-Fluorouracil; Resistance; Thymidylate synthase; Colorectal cancer; EXPRESSION PROFILE; CELLS; CHEMOSENSITIVITY; IDENTIFICATION; CHEMOTHERAPY; SENSITIVITY;
D O I
10.1007/s12094-015-1318-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The response rate of first-line fluoropyrimidine-based regimens for metastatic colorectal cancer (mCRC) is generally less than 50 %. The down-regulation of miR-197 in colorectal cancer cells after exposure to 5-fluorouracil might be related to the mechanism of resistance to fluoropyrimidine-based chemotherapy. So we investigated the regulatory mechanism of miR-197 on 5-FU sensitivity. Dual luciferase reporter gene construct and dual luciferase reporter assay were used to identify the target of miR-197. TYMS expression was evaluated by immunohistochemistry staining. 5-Fu resistance of colorectal cancer cell lines was detected by MTS assay. The expression of miR-197 was detected by real time PCR. A luciferase assay and western blot analysis confirmed that miR-197 directly binds to and negatively regulates TYMS expression. Overexpressing miR-197 could increase the sensitivity of colorectal cancer cells to 5-fluorouracil (5-FU). The expression of miR-197 negatively correlated with TYMS expression in cancerous tissues from patients with stage IV colorectal cancer. miR-197 mediates the response of colorectal cancer cells to 5-FU by regulating TYMS expression.
引用
收藏
页码:876 / 883
页数:8
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