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

• DOI: 10.1007/s12094-015-1318-7
• Publication Date: 2015-06-08T09:04:55Z
• Authors: Z. Sun; N. Zhou; Q. Han; L. Zhao; C. Bai; Y. Chen; J. Zhou; R. C. Zhao
• Keywords: Antimetabolites, Antineoplastic; 0303 health sciences; Blotting, Western; Thymidylate Synthase; Real-Time Polymerase Chain Reaction; Transfection; Immunohistochemistry; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Drug Resistance, Neoplasm; Cell Line, Tumor; Humans; Fluorouracil; RNA, Small Interfering; Colorectal Neoplasms

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.