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International Journal of Oncology
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Article

p53/microRNA-374b/AKT1 regulates colorectal cancer cell apoptosis in response to DNA damage

  • Authors:
    • Hangjun Gong
    • Yu Cao
    • Gang Han
    • Yun Zhang
    • Qing You
    • Yidong Wang
    • Yamin Pan
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China, The First Department of Endoscopy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
  • Pages: 1785-1791
    |
    Published online on: March 21, 2017
       https://doi.org/10.3892/ijo.2017.3922
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Abstract

Colorectal cancer (CRC) has a rising morbidity worldwide and its resistance to chemotherapy has been observed in clinical treatment. Tumor suppressor p53 is well-studied in CRC, but little is known about its effects during DNA damage of CRC cells. This study was aimed at uncovering potential mechanisms of p53 regarding microRNA-374b and v-akt murine thymoma viral oncogene homolog 1 (AKT1) during DNA damage of CRC cells. CRC cells HCT116 and HT29 were transfected with p53-specific small interfering RNA (siRNA), p53 overexpression vector or miR-374b inhibitor, and then treated with 10 µM bleomycin (BLM) for 24 h to induce DNA damage. Primary (pri), precursor (pre) and mature miR-374b levels were quantified by qRT-PCR. AKT1 and p53 protein levels were detected by western blotting. Cell apoptosis changes were assessed by flow cytometry. AKT1 mRNA was detected to be induced by BLM treatment (P<0.05), but its protein level was strongly inhibited. Knockdown of p53 reversed the inhibition of AKT1 protein by BLM. Overexpression of p53 in p53-knockout HCT116 and HT29 cells upregulated the AKT1 regulator miR-374b (P<0.05), and knockdown of p53 reversed the induction of miR-374b by BLM. qRT-PCR suggested that besides mature miR-374b, p53 could also promote pre-miR-374b level (P<0.05), rather than pri-miR-374b. Moreover, inhibition on miR-374b relieved the suppressed AKT1 protein, and reduced cell apoptosis induced by BLM. These data depict the p53/miR-374b/AKT1 signaling that may regulate BLM-induced apoptosis in CRC cells, thus facilitating to improve the outcome of chemotherapy in CRC.
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Copy and paste a formatted citation
Spandidos Publications style
Gong H, Cao Y, Han G, Zhang Y, You Q, Wang Y and Pan Y: p53/microRNA-374b/AKT1 regulates colorectal cancer cell apoptosis in response to DNA damage. Int J Oncol 50: 1785-1791, 2017.
APA
Gong, H., Cao, Y., Han, G., Zhang, Y., You, Q., Wang, Y., & Pan, Y. (2017). p53/microRNA-374b/AKT1 regulates colorectal cancer cell apoptosis in response to DNA damage. International Journal of Oncology, 50, 1785-1791. https://doi.org/10.3892/ijo.2017.3922
MLA
Gong, H., Cao, Y., Han, G., Zhang, Y., You, Q., Wang, Y., Pan, Y."p53/microRNA-374b/AKT1 regulates colorectal cancer cell apoptosis in response to DNA damage". International Journal of Oncology 50.5 (2017): 1785-1791.
Chicago
Gong, H., Cao, Y., Han, G., Zhang, Y., You, Q., Wang, Y., Pan, Y."p53/microRNA-374b/AKT1 regulates colorectal cancer cell apoptosis in response to DNA damage". International Journal of Oncology 50, no. 5 (2017): 1785-1791. https://doi.org/10.3892/ijo.2017.3922
Copy and paste a formatted citation
x
Spandidos Publications style
Gong H, Cao Y, Han G, Zhang Y, You Q, Wang Y and Pan Y: p53/microRNA-374b/AKT1 regulates colorectal cancer cell apoptosis in response to DNA damage. Int J Oncol 50: 1785-1791, 2017.
APA
Gong, H., Cao, Y., Han, G., Zhang, Y., You, Q., Wang, Y., & Pan, Y. (2017). p53/microRNA-374b/AKT1 regulates colorectal cancer cell apoptosis in response to DNA damage. International Journal of Oncology, 50, 1785-1791. https://doi.org/10.3892/ijo.2017.3922
MLA
Gong, H., Cao, Y., Han, G., Zhang, Y., You, Q., Wang, Y., Pan, Y."p53/microRNA-374b/AKT1 regulates colorectal cancer cell apoptosis in response to DNA damage". International Journal of Oncology 50.5 (2017): 1785-1791.
Chicago
Gong, H., Cao, Y., Han, G., Zhang, Y., You, Q., Wang, Y., Pan, Y."p53/microRNA-374b/AKT1 regulates colorectal cancer cell apoptosis in response to DNA damage". International Journal of Oncology 50, no. 5 (2017): 1785-1791. https://doi.org/10.3892/ijo.2017.3922
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