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Article

Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells

  • Authors:
    • Fang Yu
    • Liang Jin
    • Guodong Yang
    • Lin Ji
    • Feng Wang
    • Zifan Lu
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an 710032, P.R. China, Department of Toxicology, The Fourth Military Medical University, Xi'an 710032, P.R. China, Department of Nutrition and Food Hygiene, The Fourth Military Medical University, Xi'an 710032, P.R. China
  • Pages: 1459-1465
    |
    Published online on: December 31, 2013
       https://doi.org/10.3892/or.2013.2957
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Abstract

The RNA-binding protein Quaking (QKI) is known to be essential for embryonic development and postnatal myelination. Forkhead box O1 (FOXO1) is a critical tumor suppressor for cell proliferation control. Dysregulation of FOXO1 expression has been observed in a variety of cancers. In the present study, we demonstrated that QKI decreased FOXO1 mRNA expression at the post-transcriptional level. QKI was able to bind the 3'UTR of FOXO1 mRNA directly and decreased its mRNA stability. To determine whether QKI-mediated post-transcriptional repression of FOXO1 indeed plays a role in cancer cells, we first detected both QKI and FOXO1 expression in four breast cancer cell lines. FOXO1 expression was extremely low in these cell lines, whereas QKI expression was relative high. Knockdown of QKI significantly restored FOXO1 expression. ATRA, an inducer of apoptosis or differentiation, dramatically enhanced FOXO1 expression while it repressed QKI expression. Importantly, the ATRA-induced increase in FOXO1 expression was dependent on QKI-mediated post-transcriptional regulation. Consistently, 5-FU, a widely used chemotherapeutic agent, increased FOXO1 expression via inhibition of QKI. In summary, our study provides initial evidence demonstrating that QKI-mediated repression of FOXO1 may be one of the factors contributing to the oncogenesis and progression of breast carcinoma, which suggests that targeting QKI may serve as a novel strategy to sensitize breast cancers to chemotherapy.
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Copy and paste a formatted citation
Spandidos Publications style
Yu F, Jin L, Yang G, Ji L, Wang F and Lu Z: Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells. Oncol Rep 31: 1459-1465, 2014.
APA
Yu, F., Jin, L., Yang, G., Ji, L., Wang, F., & Lu, Z. (2014). Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells. Oncology Reports, 31, 1459-1465. https://doi.org/10.3892/or.2013.2957
MLA
Yu, F., Jin, L., Yang, G., Ji, L., Wang, F., Lu, Z."Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells". Oncology Reports 31.3 (2014): 1459-1465.
Chicago
Yu, F., Jin, L., Yang, G., Ji, L., Wang, F., Lu, Z."Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells". Oncology Reports 31, no. 3 (2014): 1459-1465. https://doi.org/10.3892/or.2013.2957
Copy and paste a formatted citation
x
Spandidos Publications style
Yu F, Jin L, Yang G, Ji L, Wang F and Lu Z: Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells. Oncol Rep 31: 1459-1465, 2014.
APA
Yu, F., Jin, L., Yang, G., Ji, L., Wang, F., & Lu, Z. (2014). Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells. Oncology Reports, 31, 1459-1465. https://doi.org/10.3892/or.2013.2957
MLA
Yu, F., Jin, L., Yang, G., Ji, L., Wang, F., Lu, Z."Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells". Oncology Reports 31.3 (2014): 1459-1465.
Chicago
Yu, F., Jin, L., Yang, G., Ji, L., Wang, F., Lu, Z."Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells". Oncology Reports 31, no. 3 (2014): 1459-1465. https://doi.org/10.3892/or.2013.2957
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