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

Chai,Zongtao; Yin,Xiaolan; Chen,Jin; Shi,Jie; Sun,Juxian; Liu,Chang; Liu,Feng; Cheng,Shuqun

doi:10.3892/ol.2019.10674

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
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Affiliations: Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, P.R. China, Precision Medical Center, Shanghai Hospital, Second Military Medical University, Shanghai 200433, P.R. China
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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