MiR-122 Reverses the Doxorubicin-Resistance in Hepatocellular Carcinoma Cells through Regulating the Tumor Metabolism

Doxorubicin (DOX) is one of the most commonly used anticancer drugs in the treatment of hepatoma. However, acquired drug resistance is one of the major challenges for the chemotherapy. In this study, a down-regulation of miR-122 was observed in doxorubicin-resistant Huh7 (Huh7/R) cells compared with...

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Bibliographic Details
Published in:PloS one 2016-05, Vol.11 (5), p.e0152090-e0152090
Main Authors: Pan, Chenwei, Wang, Xiaodong, Shi, Keqing, Zheng, Yi, Li, Jie, Chen, Yongping, Jin, Lingxiang, Pan, Zhenzhen
Format: Article
Language:English
Subjects:
Antibiotics, Antineoplastic - therapeutic use
Antineoplastic drugs
Antitumor agents
Apoptosis
Biology and Life Sciences
Cancer therapies
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Cell growth
Cell Line
Chemoresistance
Chemotherapy
Comparative analysis
Complications and side effects
Cytotoxicity
Dosage and administration
Doxorubicin
Doxorubicin - therapeutic use
Drug resistance
Drug Resistance, Neoplasm - genetics
Drug therapy
Drugs
Gene expression
Genetic aspects
Glucose
Glucose metabolism
Glycolysis
Health aspects
Hepatocellular carcinoma
Hepatoma
Humans
Infectious diseases
Inhibition
Kinases
Liver cancer
Liver Neoplasms - drug therapy
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Medical prognosis
Medicine and Health Sciences
Metabolism
Metastasis
MicroRNA
MicroRNAs
MicroRNAs - genetics
MicroRNAs - physiology
Physiological aspects
Research and Analysis Methods
Studies
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Summary:Doxorubicin (DOX) is one of the most commonly used anticancer drugs in the treatment of hepatoma. However, acquired drug resistance is one of the major challenges for the chemotherapy. In this study, a down-regulation of miR-122 was observed in doxorubicin-resistant Huh7 (Huh7/R) cells compared with its parental Huh7 cells, suggesting miR-122 is associated with the chemoresistance. Meanwhile, luciferase reporter assay proved that the PKM2 is the target of miR-122, and we reported that the glucose metabolism is significantly up-regulated in Huh7/R cells. Importantly, overexpression of miR-122 in Huh7/R cells reversed the doxorubicin-resistance through the inhibition of PKM2, inducing the apoptosis in doxorubicin-resistant cancer cells. Thus, this study revealed that the dysregulated glucose metabolism contributes to doxorubicin resistance, and the inhibition of glycolysis induced by miR-122 might be a promising therapeutic strategy to overcome doxorubicin resistance in hepatocellular carcinoma.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0152090