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Inhibition of Lon blocks cell proliferation, enhances chemosensitivity by promoting apoptosis and decreases cellular bioenergetics of bladder cancer: potential roles of Lon as a prognostic marker and therapeutic target in baldder cancer

ATP-dependent Lon protease within mitochondrial matrix contributes to the degradation of abnormal proteins. The oxidative or hypoxic stress which represents the stress phenotype of cancer leads to up-regulation of Lon. However, the role of Lon in bladder cancer remains undefined. Here, we found that...

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Autores principales: Liu, Yongzhang, Lan, Linhua, Huang, Kate, Wang, Rongrong, Xu, Cuicui, Shi, Yang, Wu, Xiaoyi, Wu, Zhi, Zhang, Jiliang, Chen, Lin, Wang, Lu, Yu, Xiaomin, Zhu, Haibo, Lu, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294382/
https://www.ncbi.nlm.nih.gov/pubmed/25526030
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author Liu, Yongzhang
Lan, Linhua
Huang, Kate
Wang, Rongrong
Xu, Cuicui
Shi, Yang
Wu, Xiaoyi
Wu, Zhi
Zhang, Jiliang
Chen, Lin
Wang, Lu
Yu, Xiaomin
Zhu, Haibo
Lu, Bin
author_facet Liu, Yongzhang
Lan, Linhua
Huang, Kate
Wang, Rongrong
Xu, Cuicui
Shi, Yang
Wu, Xiaoyi
Wu, Zhi
Zhang, Jiliang
Chen, Lin
Wang, Lu
Yu, Xiaomin
Zhu, Haibo
Lu, Bin
author_sort Liu, Yongzhang
collection PubMed
description ATP-dependent Lon protease within mitochondrial matrix contributes to the degradation of abnormal proteins. The oxidative or hypoxic stress which represents the stress phenotype of cancer leads to up-regulation of Lon. However, the role of Lon in bladder cancer remains undefined. Here, we found that Lon expression in bladder cancer tissues was significantly higher than those in noncancerous tissues; down-regulation of Lon in bladder cancer cells significantly blocked cancer cell proliferation via suppression c-Jun N-terminal kinase (JNK) phosphorylation due to decreased reactive oxygen species (ROS) production and enhanced the sensitivity of bladder cancer cells to chemotherapeutic agents by promoting apoptosis. We further found that Lon down-regulation in bladder cancer cells decreased cellular bioenergetics as determined by measuring aerobic respiration and glycolysis using extracellular flux analyzer. The tissue microarray (TMA) results showed that high expression of Lon was related to the T and TNM stage, as well as histological grade of bladder cancer patients. We also demonstrated that Lon was an independent prognostic factor for overall survival of bladder cancer. Taken together, our data suggest that Lon could serve as a potential diagnostic biomarker and therapeutic target for treatment of bladder cancer, as well as for prediction of the effectiveness of chemotherapy.
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spelling pubmed-42943822015-01-21 Inhibition of Lon blocks cell proliferation, enhances chemosensitivity by promoting apoptosis and decreases cellular bioenergetics of bladder cancer: potential roles of Lon as a prognostic marker and therapeutic target in baldder cancer Liu, Yongzhang Lan, Linhua Huang, Kate Wang, Rongrong Xu, Cuicui Shi, Yang Wu, Xiaoyi Wu, Zhi Zhang, Jiliang Chen, Lin Wang, Lu Yu, Xiaomin Zhu, Haibo Lu, Bin Oncotarget Research Paper ATP-dependent Lon protease within mitochondrial matrix contributes to the degradation of abnormal proteins. The oxidative or hypoxic stress which represents the stress phenotype of cancer leads to up-regulation of Lon. However, the role of Lon in bladder cancer remains undefined. Here, we found that Lon expression in bladder cancer tissues was significantly higher than those in noncancerous tissues; down-regulation of Lon in bladder cancer cells significantly blocked cancer cell proliferation via suppression c-Jun N-terminal kinase (JNK) phosphorylation due to decreased reactive oxygen species (ROS) production and enhanced the sensitivity of bladder cancer cells to chemotherapeutic agents by promoting apoptosis. We further found that Lon down-regulation in bladder cancer cells decreased cellular bioenergetics as determined by measuring aerobic respiration and glycolysis using extracellular flux analyzer. The tissue microarray (TMA) results showed that high expression of Lon was related to the T and TNM stage, as well as histological grade of bladder cancer patients. We also demonstrated that Lon was an independent prognostic factor for overall survival of bladder cancer. Taken together, our data suggest that Lon could serve as a potential diagnostic biomarker and therapeutic target for treatment of bladder cancer, as well as for prediction of the effectiveness of chemotherapy. Impact Journals LLC 2014-05-28 /pmc/articles/PMC4294382/ /pubmed/25526030 Text en Copyright: © 2014 Liu et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Liu, Yongzhang
Lan, Linhua
Huang, Kate
Wang, Rongrong
Xu, Cuicui
Shi, Yang
Wu, Xiaoyi
Wu, Zhi
Zhang, Jiliang
Chen, Lin
Wang, Lu
Yu, Xiaomin
Zhu, Haibo
Lu, Bin
Inhibition of Lon blocks cell proliferation, enhances chemosensitivity by promoting apoptosis and decreases cellular bioenergetics of bladder cancer: potential roles of Lon as a prognostic marker and therapeutic target in baldder cancer
title Inhibition of Lon blocks cell proliferation, enhances chemosensitivity by promoting apoptosis and decreases cellular bioenergetics of bladder cancer: potential roles of Lon as a prognostic marker and therapeutic target in baldder cancer
title_full Inhibition of Lon blocks cell proliferation, enhances chemosensitivity by promoting apoptosis and decreases cellular bioenergetics of bladder cancer: potential roles of Lon as a prognostic marker and therapeutic target in baldder cancer
title_fullStr Inhibition of Lon blocks cell proliferation, enhances chemosensitivity by promoting apoptosis and decreases cellular bioenergetics of bladder cancer: potential roles of Lon as a prognostic marker and therapeutic target in baldder cancer
title_full_unstemmed Inhibition of Lon blocks cell proliferation, enhances chemosensitivity by promoting apoptosis and decreases cellular bioenergetics of bladder cancer: potential roles of Lon as a prognostic marker and therapeutic target in baldder cancer
title_short Inhibition of Lon blocks cell proliferation, enhances chemosensitivity by promoting apoptosis and decreases cellular bioenergetics of bladder cancer: potential roles of Lon as a prognostic marker and therapeutic target in baldder cancer
title_sort inhibition of lon blocks cell proliferation, enhances chemosensitivity by promoting apoptosis and decreases cellular bioenergetics of bladder cancer: potential roles of lon as a prognostic marker and therapeutic target in baldder cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294382/
https://www.ncbi.nlm.nih.gov/pubmed/25526030
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