A let-7b binding site SNP in the 3'-UTR of the Bcl-xL gene enhances resistance to 5-fluorouracil and doxorubicin in breast cancer cells

  • Authors:
    • Ting Wang
    • Bin Huang
    • Rui Guo
    • Jin Ma
    • Cuiying Peng
    • Xuyu Zu
    • Huifang Tang
    • Xiaoyong Lei
  • View Affiliations

  • Published online on: February 6, 2015     https://doi.org/10.3892/ol.2015.2938
  • Pages: 1907-1911
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Abstract

The development of acquired resistance to chemotherapy is a major obstacle in the successful treatment of cancer. In breast cancer cells, B‑cell lymphoma‑extra large (Bcl‑xL) is involved in the development of resistance to various chemotherapeutic agents; therefore, preliminary biological prediction was performed to identify a putative binding site for let‑7b in the 3'‑untranslated region (UTR) of the Bcl‑xL gene and a single nucleotide polymorphism (SNP) within this binding region. The present study investigated the association between the SNP rs3208684 A>C and chemotherapeutic agent resistance in breast cancer cells. The data indicated that let‑7b negatively regulates the expression of Bcl‑xL and appears to sensitize MCF‑7 cells to the chemotherapeutic agents 5‑fluorouracil (5‑FU) and doxorubicin. Furthermore, the SNP rs3208684 A>C was demonstrated to enhance Bcl‑xL protein expression by disrupting the binding of let‑7b to the 3'‑UTR of Bcl‑xL and, in MCF‑7 cells, overexpression of let‑7b in the presence of a mutant Bcl‑xL 3'‑UTR (C allele) significantly increased 5‑FU and doxorubicin resistance. Thus, the results of the present study demonstrate that the SNP rs3208684 A>C may upregulate Bcl‑xL protein expression and enhance the resistance of the MCF‑7 cells to 5‑FU and doxorubicin by decreasing the binding of let‑7b to the 3'‑UTR of Bcl‑xL.
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April-2015
Volume 9 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Wang T, Huang B, Guo R, Ma J, Peng C, Zu X, Tang H and Lei X: A let-7b binding site SNP in the 3'-UTR of the Bcl-xL gene enhances resistance to 5-fluorouracil and doxorubicin in breast cancer cells. Oncol Lett 9: 1907-1911, 2015.
APA
Wang, T., Huang, B., Guo, R., Ma, J., Peng, C., Zu, X. ... Lei, X. (2015). A let-7b binding site SNP in the 3'-UTR of the Bcl-xL gene enhances resistance to 5-fluorouracil and doxorubicin in breast cancer cells. Oncology Letters, 9, 1907-1911. https://doi.org/10.3892/ol.2015.2938
MLA
Wang, T., Huang, B., Guo, R., Ma, J., Peng, C., Zu, X., Tang, H., Lei, X."A let-7b binding site SNP in the 3'-UTR of the Bcl-xL gene enhances resistance to 5-fluorouracil and doxorubicin in breast cancer cells". Oncology Letters 9.4 (2015): 1907-1911.
Chicago
Wang, T., Huang, B., Guo, R., Ma, J., Peng, C., Zu, X., Tang, H., Lei, X."A let-7b binding site SNP in the 3'-UTR of the Bcl-xL gene enhances resistance to 5-fluorouracil and doxorubicin in breast cancer cells". Oncology Letters 9, no. 4 (2015): 1907-1911. https://doi.org/10.3892/ol.2015.2938