Open Access

MicroRNA‑101 modulates cisplatin chemoresistance in liver cancer cells via the DNA‑PKcs signaling pathway

  • Authors:
    • Zongtao Chai
    • Xiaolan Yin
    • Jin Chen
    • Jie Shi
    • Juxian Sun
    • Chang Liu
    • Feng Liu
    • Shuqun Cheng
  • View Affiliations

  • Published online on: July 26, 2019     https://doi.org/10.3892/ol.2019.10674
  • Pages: 3655-3663
  • Copyright: © Chai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Due to the high incidence of liver cancer, chemoradiotherapy and prognosis of liver cancer are a primary focus of medical research. microRNAs (miRNAs/miRs) serve crucial roles in resistance to chemotherapy and radiotherapy. The aim of the present study was to investigate the effects of miR‑101 on the chemotherapeutic efficacy of cisplatin (CDDP) in liver cancer. First, human liver cancer cells (HepG2) were transfected with a miR‑101 mimic or miR‑101 inhibitor to bidirectionally regulate the expression of miR‑101. Cell proliferation, apoptosis, intracellular reactive oxygen species and comet assay results indicated that the upregulation of miR‑101 sensitized HepG2 cells to CDDP, and downregulation of miR‑101 reduced chemosensitivity. A xenograft mouse model further confirmed that miR‑101 overexpression increased CDDP sensitivity in liver cancer. Luciferase reporter and western blotting assays demonstrated that transfection of the miR‑101 mimic markedly reduced activity of the DNA‑dependent protein kinase catalytic subunit/protein kinase B/mammalian target of rapamycin (DNA‑PKcs/Akt/mTOR) pathway and increased expression of apoptotic protein caspase 3, which is induced by CDDP treatment. By contrast, miR‑101 inhibitors partially reversed these changes. Moreover, the miR‑101 mimic suppressed activity of the nuclear factor‑κB (NF‑κB) pathway, leading to increased susceptibility of HepG2 cells to chemotherapeutic agents. In conclusion, miR‑101 overexpression augmented cytotoxicity and reduced chemoresistance to CDDP in HepG2 cells, and this was associated with negative regulation of DNA‑PKcs/Akt/NF‑κB signaling.

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October 2019
Volume 18 Issue 4

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

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Copy and paste a formatted citation
APA
Chai, Z., Yin, X., Chen, J., Shi, J., Sun, J., Liu, C. ... Cheng, S. (2019). MicroRNA‑101 modulates cisplatin chemoresistance in liver cancer cells via the DNA‑PKcs signaling pathway. Oncology Letters, 18, 3655-3663. https://doi.org/10.3892/ol.2019.10674
MLA
Chai, Z., Yin, X., Chen, J., Shi, J., Sun, J., Liu, C., Liu, F., Cheng, S."MicroRNA‑101 modulates cisplatin chemoresistance in liver cancer cells via the DNA‑PKcs signaling pathway". Oncology Letters 18.4 (2019): 3655-3663.
Chicago
Chai, Z., Yin, X., Chen, J., Shi, J., Sun, J., Liu, C., Liu, F., Cheng, S."MicroRNA‑101 modulates cisplatin chemoresistance in liver cancer cells via the DNA‑PKcs signaling pathway". Oncology Letters 18, no. 4 (2019): 3655-3663. https://doi.org/10.3892/ol.2019.10674