A miR-26a/E2F7 feedback loop contributes to tamoxifen resistance in ER-positive breast cancer

  • Authors:
    • Jian Liu
    • Xiang Li
    • Meng Wang
    • Guodong Xiao
    • Ganghua Yang
    • Huangzhen Wang
    • Yanbo Li
    • Xin Sun
    • Sida Qin
    • Ning Du
    • Hong Ren
    • Yamei Pang
  • View Affiliations

  • Published online on: July 19, 2018     https://doi.org/10.3892/ijo.2018.4492
  • Pages: 1601-1612
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Abstract

Tamoxifen (TAM) resistance is a substantial challenge in the treatment of estrogen receptor (ER)-positive breast cancer. Previous studies have revealed an important role of microRNA (miRNA/miR)-26a in TAM resistance in breast cancer. However, the mechanism underlying the regulatory effects of miR-26a on TAM resistance remains to be elucidated. The expression levels of miR-26a in ER-positive breast cancer were detected by reverse transcription-quantitative polymerase chain reaction. E2F transcription factor 7 (E2F7) and MYC proto-oncogene, bHLH transcription factor (MYC) levels were detected by western blotting. The present study demonstrated that miR-26a expression was reduced in ER-positive breast cancer compared with in normal breast tissues, whereas E2F7 expression was significantly elevated. Furthermore, an inverse correlation between miR-26a and E2F7 expression was detected in ER-positive breast cancer. The results indicated that miR-26a directly inhibited E2F7 expression through translational inhibition and indirectly inhibited MYC expression partly via E2F7 repression. E2F7, in turn, decreased miR-26a expression via MYC-induced transcriptional inhibition of miRNAs. Furthermore, transfection with miR-26a mimics increased the expression of its host genes (CTD small phosphatase like and CTD small phosphatase 2), whereas ectopic E2F7 expression abrogated the effects of miR-26a. These findings indicated that miR-26a and E2F7 may form a double-negative feedback loop, resulting in downregulation of miR-26a and upregulation of E2F7 in ER-positive breast cancer. Both miR-26a knockdown and E2F7 overexpression conferred resistance to TAM in MCF-7 cells. Conversely, miR-26a overexpression and E2F7 silencing resensitized MCF-7 resistant cells to TAM. These findings revealed that a feedback loop between miR-26a and E2F7 may promote TAM resistance in ER-positive breast cancer.

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Copy and paste a formatted citation
APA
Liu, J., Li, X., Wang, M., Xiao, G., Yang, G., Wang, H. ... Pang, Y. (2018). A miR-26a/E2F7 feedback loop contributes to tamoxifen resistance in ER-positive breast cancer. International Journal of Oncology, 53, 1601-1612. https://doi.org/10.3892/ijo.2018.4492
MLA
Liu, J., Li, X., Wang, M., Xiao, G., Yang, G., Wang, H., Li, Y., Sun, X., Qin, S., Du, N., Ren, H., Pang, Y."A miR-26a/E2F7 feedback loop contributes to tamoxifen resistance in ER-positive breast cancer". International Journal of Oncology 53.4 (2018): 1601-1612.
Chicago
Liu, J., Li, X., Wang, M., Xiao, G., Yang, G., Wang, H., Li, Y., Sun, X., Qin, S., Du, N., Ren, H., Pang, Y."A miR-26a/E2F7 feedback loop contributes to tamoxifen resistance in ER-positive breast cancer". International Journal of Oncology 53, no. 4 (2018): 1601-1612. https://doi.org/10.3892/ijo.2018.4492