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.