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
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  • Published online on: March 21, 2017     https://doi.org/10.3892/ijo.2017.3922
  • Pages: 1785-1791
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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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May-2017
Volume 50 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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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