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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2018-10-01
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doaj-cdfef97ff7f24220bae98bac8348f41f2020-11-25T03:28:29ZengElsevierRedox Biology2213-23172018-10-0119412428Myostatin knockout induces apoptosis in human cervical cancer cells via elevated reactive oxygen species generationYing-Qian Han0Sheng-Li Ming1Hong-Tao Wu2Lei Zeng3Gen Ba4Jian Li5Wei-Fei Lu6Jie Han7Qia-Jun Du8Miao-Miao Sun9Guo-Yu Yang10Jiang Wang11Bei-Bei Chu12College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR ChinaCollege of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR ChinaCollege of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR ChinaCollege of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR ChinaCollege of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR ChinaCollege of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR ChinaCollege of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR China; Department of Radiology, University of Michigan, Ann Arbor, MI 48109-2200, USADepartment of Endocrinology, the First Hospital of Lanzhou University, Lanzhou, Gansu Province, PR ChinaClinical Laboratory, the Second Hospital of Lanzhou University, Lanzhou, Gansu Province, PR ChinaThe Pathology Department of the Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, Henan Province, PR ChinaCollege of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR China; Corresponding authors.College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR China; Corresponding authors.College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR China; Corresponding authors.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. Keywords: Myostatin, CRISPR/Cas9, Apoptosis, Reactive oxygen specieshttp://www.sciencedirect.com/science/article/pii/S2213231718306888 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ying-Qian Han Sheng-Li Ming Hong-Tao Wu Lei Zeng Gen Ba Jian Li Wei-Fei Lu Jie Han Qia-Jun Du Miao-Miao Sun Guo-Yu Yang Jiang Wang Bei-Bei Chu |
spellingShingle |
Ying-Qian Han Sheng-Li Ming Hong-Tao Wu Lei Zeng Gen Ba Jian Li Wei-Fei Lu Jie Han Qia-Jun Du Miao-Miao Sun Guo-Yu Yang Jiang Wang Bei-Bei Chu Myostatin knockout induces apoptosis in human cervical cancer cells via elevated reactive oxygen species generation Redox Biology |
author_facet |
Ying-Qian Han Sheng-Li Ming Hong-Tao Wu Lei Zeng Gen Ba Jian Li Wei-Fei Lu Jie Han Qia-Jun Du Miao-Miao Sun Guo-Yu Yang Jiang Wang Bei-Bei Chu |
author_sort |
Ying-Qian Han |
title |
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_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_sort |
myostatin knockout induces apoptosis in human cervical cancer cells via elevated reactive oxygen species generation |
publisher |
Elsevier |
series |
Redox Biology |
issn |
2213-2317 |
publishDate |
2018-10-01 |
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. Keywords: Myostatin, CRISPR/Cas9, Apoptosis, Reactive oxygen species |
url |
http://www.sciencedirect.com/science/article/pii/S2213231718306888 |
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