title: MicroRNA-197 influences 5-fluorouracil resistance via thymidylate synthase in colorectal cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  miR-197 mediates the response of colorectal cancer cells to 5-FU by regulating TYMS expression.
authors.affiliation: Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: N
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Q
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Bai
authors.affiliation: Department of Digestion, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. jianfengzhouzhou@126.com.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People's Republic of China. chunhuaz@public.tpt.tj.cn.|Center of Translational Medicine, Peking Union Medical College Hospital, Beijing, People's Republic of China. chunhuaz@public.tpt.tj.cn.
authors.forename: R C
authors.initials: RC
authors.lastname: Zhao
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005472:Fluorouracil / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D013940:Thymidylate Synthase / Q000096:biosynthesis*; D014162:Transfection
chemical_list: D000964:Antimetabolites, Antineoplastic; C546085:MIRN197 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D013940:Thymidylate Synthase; D005472:Fluorouracil
keywords: 5-Fluorouracil; Colorectal cancer; Resistance; Thymidylate synthase; miR-197