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Article

miR-203 enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer

  • Authors:
    • Tao Li
    • Feng Gao
    • Xi-Peng Zhang
  • View Affiliations / Copyright

    Affiliations: Colorectal Center, Tianjin Union Medical Center, Tianjin 300121, P.R. China, Department of General Surgery, Qingdao Hiser Medical Center, Qingdao, Shandong 266033, P.R. China
  • Pages: 607-614
    |
    Published online on: December 4, 2014
       https://doi.org/10.3892/or.2014.3646
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Abstract

MicroRNAs (miRNAs) are a conserved class of small non-coding RNAs that play important roles in diverse biological processes, including chemoresistance. However, the molecular mechanism as to how miR-203 modulates the chemosensitivity to 5-fluorouracil (5-FU) in colorectal cancer is poorly known. In the present study, we found that miR-203 was downregulated in the 5-FU-resistant cell line LoVo/5-Fu, and was inversely correlated with the extent of 5-FU chemoresistance. Cytotoxicity assay showed that the inhibition of miR-203 expression enhanced 5-FU chemoresistance in colorectal cancer cells, while miR-203 overexpression increased 5-FU chemosensitivity. We then validated that thymidylate synthase (TYMS) was a direct target of miR-203 and miR-203 suppressed TYMS protein levels. Silencing of TYMS enhanced 5-FU chemosensitivity, similar to the roles of miR-203. Finally, we discovered that miR-203 increased the inhibitory effects of 5-FU on tumor growth in vivo. Overall, our data indicate that miR-203 enhances 5-FU chemosensitivity via the downregulation of TYMS in colorectal cancer and provide important insight into the mechanism of 5-FU resistance in colorectal cancer patients. More important, the present study suggests that miR-203 has the potential as a therapeutic strategy for 5-FU-resistant colorectal cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Li T, Gao F and Zhang X: miR-203 enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer. Oncol Rep 33: 607-614, 2015.
APA
Li, T., Gao, F., & Zhang, X. (2015). miR-203 enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer. Oncology Reports, 33, 607-614. https://doi.org/10.3892/or.2014.3646
MLA
Li, T., Gao, F., Zhang, X."miR-203 enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer". Oncology Reports 33.2 (2015): 607-614.
Chicago
Li, T., Gao, F., Zhang, X."miR-203 enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer". Oncology Reports 33, no. 2 (2015): 607-614. https://doi.org/10.3892/or.2014.3646
Copy and paste a formatted citation
x
Spandidos Publications style
Li T, Gao F and Zhang X: miR-203 enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer. Oncol Rep 33: 607-614, 2015.
APA
Li, T., Gao, F., & Zhang, X. (2015). miR-203 enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer. Oncology Reports, 33, 607-614. https://doi.org/10.3892/or.2014.3646
MLA
Li, T., Gao, F., Zhang, X."miR-203 enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer". Oncology Reports 33.2 (2015): 607-614.
Chicago
Li, T., Gao, F., Zhang, X."miR-203 enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer". Oncology Reports 33, no. 2 (2015): 607-614. https://doi.org/10.3892/or.2014.3646
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