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Myostatin knockout induces apoptosis in human cervical cancer cells via elevated reactive oxygen species generation

Myostatin (Mstn) is postulated to be a key determinant of muscle loss and cachexia in cancer. However, no experimental evidence supports a role for Mstn in cancer, particularly in regulating the survival and growth of cancer cells. In this study, we showed that the expression of Mstn was significant...

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Autores principales: Han, Ying-Qian, Ming, Sheng-Li, Wu, Hong-Tao, Zeng, Lei, Ba, Gen, Li, Jian, Lu, Wei-Fei, Han, Jie, Du, Qia-Jun, Sun, Miao-Miao, Yang, Guo-Yu, Wang, Jiang, Chu, Bei-Bei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146590/
https://www.ncbi.nlm.nih.gov/pubmed/30241032
http://dx.doi.org/10.1016/j.redox.2018.09.009
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author Han, Ying-Qian
Ming, Sheng-Li
Wu, Hong-Tao
Zeng, Lei
Ba, Gen
Li, Jian
Lu, Wei-Fei
Han, Jie
Du, Qia-Jun
Sun, Miao-Miao
Yang, Guo-Yu
Wang, Jiang
Chu, Bei-Bei
author_facet Han, Ying-Qian
Ming, Sheng-Li
Wu, Hong-Tao
Zeng, Lei
Ba, Gen
Li, Jian
Lu, Wei-Fei
Han, Jie
Du, Qia-Jun
Sun, Miao-Miao
Yang, Guo-Yu
Wang, Jiang
Chu, Bei-Bei
author_sort Han, Ying-Qian
collection PubMed
description Myostatin (Mstn) is postulated to be a key determinant of muscle loss and cachexia in cancer. However, no experimental evidence supports a role for Mstn in cancer, particularly in regulating the survival and growth of cancer cells. In this study, we showed that the expression of Mstn was significantly increased in different tumor tissues and human cancer cells. Mstn knockdown inhibited the proliferation of cancer cells. A knockout (KO) of Mstn created by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) 9 (CRISPR/Cas9) induced mitochondria-dependent apoptosis in HeLa cells. Furthermore, KO of Mstn reduced the lipid content. Molecular analyses demonstrated that the expression levels of fatty acid oxidation-related genes were upregulated and then increased rate of fatty acid oxidation. Mstn deficiency-induced apoptosis took place along with generation of reactive oxygen species (ROS) and elevated fatty acid oxidation, which may play a role in triggering mitochondrial membrane depolarization, the release of cytochrome c (Cyt-c), and caspase activation. Importantly, apoptosis induced by Mstn KO was partially rescued by antioxidants and etomoxir, thereby suggesting that the increased level of ROS was functionally involved in mediating apoptosis. Overall, our findings demonstrate a novel function of Mstn in regulating mitochondrial metabolism and apoptosis within cancer cells. Hence, inhibiting the production and function of Mstn may be an effective therapeutic intervention during cancer progression and muscle loss in cachexia.
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spelling pubmed-61465902018-09-21 Myostatin knockout induces apoptosis in human cervical cancer cells via elevated reactive oxygen species generation Han, Ying-Qian Ming, Sheng-Li Wu, Hong-Tao Zeng, Lei Ba, Gen Li, Jian Lu, Wei-Fei Han, Jie Du, Qia-Jun Sun, Miao-Miao Yang, Guo-Yu Wang, Jiang Chu, Bei-Bei Redox Biol Research Paper Myostatin (Mstn) is postulated to be a key determinant of muscle loss and cachexia in cancer. However, no experimental evidence supports a role for Mstn in cancer, particularly in regulating the survival and growth of cancer cells. In this study, we showed that the expression of Mstn was significantly increased in different tumor tissues and human cancer cells. Mstn knockdown inhibited the proliferation of cancer cells. A knockout (KO) of Mstn created by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) 9 (CRISPR/Cas9) induced mitochondria-dependent apoptosis in HeLa cells. Furthermore, KO of Mstn reduced the lipid content. Molecular analyses demonstrated that the expression levels of fatty acid oxidation-related genes were upregulated and then increased rate of fatty acid oxidation. Mstn deficiency-induced apoptosis took place along with generation of reactive oxygen species (ROS) and elevated fatty acid oxidation, which may play a role in triggering mitochondrial membrane depolarization, the release of cytochrome c (Cyt-c), and caspase activation. Importantly, apoptosis induced by Mstn KO was partially rescued by antioxidants and etomoxir, thereby suggesting that the increased level of ROS was functionally involved in mediating apoptosis. Overall, our findings demonstrate a novel function of Mstn in regulating mitochondrial metabolism and apoptosis within cancer cells. Hence, inhibiting the production and function of Mstn may be an effective therapeutic intervention during cancer progression and muscle loss in cachexia. Elsevier 2018-09-13 /pmc/articles/PMC6146590/ /pubmed/30241032 http://dx.doi.org/10.1016/j.redox.2018.09.009 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Han, Ying-Qian
Ming, Sheng-Li
Wu, Hong-Tao
Zeng, Lei
Ba, Gen
Li, Jian
Lu, Wei-Fei
Han, Jie
Du, Qia-Jun
Sun, Miao-Miao
Yang, Guo-Yu
Wang, Jiang
Chu, Bei-Bei
Myostatin knockout induces apoptosis in human cervical cancer cells via elevated reactive oxygen species generation
title Myostatin knockout induces apoptosis in human cervical cancer cells via elevated reactive oxygen species generation
title_full Myostatin knockout induces apoptosis in human cervical cancer cells via elevated reactive oxygen species generation
title_fullStr Myostatin knockout induces apoptosis in human cervical cancer cells via elevated reactive oxygen species generation
title_full_unstemmed Myostatin knockout induces apoptosis in human cervical cancer cells via elevated reactive oxygen species generation
title_short Myostatin knockout induces apoptosis in human cervical cancer cells via elevated reactive oxygen species generation
title_sort myostatin knockout induces apoptosis in human cervical cancer cells via elevated reactive oxygen species generation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146590/
https://www.ncbi.nlm.nih.gov/pubmed/30241032
http://dx.doi.org/10.1016/j.redox.2018.09.009
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