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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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Autores principales: Pan, Chenwei, Wang, Xiaodong, Shi, Keqing, Zheng, Yi, Li, Jie, Chen, Yongping, Jin, Lingxiang, Pan, Zhenzhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854441/
https://www.ncbi.nlm.nih.gov/pubmed/27138141
http://dx.doi.org/10.1371/journal.pone.0152090
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author Pan, Chenwei
Wang, Xiaodong
Shi, Keqing
Zheng, Yi
Li, Jie
Chen, Yongping
Jin, Lingxiang
Pan, Zhenzhen
author_facet Pan, Chenwei
Wang, Xiaodong
Shi, Keqing
Zheng, Yi
Li, Jie
Chen, Yongping
Jin, Lingxiang
Pan, Zhenzhen
author_sort Pan, Chenwei
collection PubMed
description 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.
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spelling pubmed-48544412016-05-07 MiR-122 Reverses the Doxorubicin-Resistance in Hepatocellular Carcinoma Cells through Regulating the Tumor Metabolism Pan, Chenwei Wang, Xiaodong Shi, Keqing Zheng, Yi Li, Jie Chen, Yongping Jin, Lingxiang Pan, Zhenzhen PLoS One Research Article 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. Public Library of Science 2016-05-03 /pmc/articles/PMC4854441/ /pubmed/27138141 http://dx.doi.org/10.1371/journal.pone.0152090 Text en © 2016 Pan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pan, Chenwei
Wang, Xiaodong
Shi, Keqing
Zheng, Yi
Li, Jie
Chen, Yongping
Jin, Lingxiang
Pan, Zhenzhen
MiR-122 Reverses the Doxorubicin-Resistance in Hepatocellular Carcinoma Cells through Regulating the Tumor Metabolism
title MiR-122 Reverses the Doxorubicin-Resistance in Hepatocellular Carcinoma Cells through Regulating the Tumor Metabolism
title_full MiR-122 Reverses the Doxorubicin-Resistance in Hepatocellular Carcinoma Cells through Regulating the Tumor Metabolism
title_fullStr MiR-122 Reverses the Doxorubicin-Resistance in Hepatocellular Carcinoma Cells through Regulating the Tumor Metabolism
title_full_unstemmed MiR-122 Reverses the Doxorubicin-Resistance in Hepatocellular Carcinoma Cells through Regulating the Tumor Metabolism
title_short MiR-122 Reverses the Doxorubicin-Resistance in Hepatocellular Carcinoma Cells through Regulating the Tumor Metabolism
title_sort mir-122 reverses the doxorubicin-resistance in hepatocellular carcinoma cells through regulating the tumor metabolism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854441/
https://www.ncbi.nlm.nih.gov/pubmed/27138141
http://dx.doi.org/10.1371/journal.pone.0152090
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