NDUFA4L2 Regulated by HIF-1α Promotes Metastasis and Epithelial–Mesenchymal Transition of Osteosarcoma Cells Through Inhibiting ROS Production
Osteosarcoma (OS) accounts for a large proportion of the types of bone tumors that are newly diagnosed, and is a relatively common bone tumor. However, there are still no effective treatments for this affliction. One interesting avenue is related to the mitochondrial NDUFA4L2 protein, which is encod...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.515051/full |
| _version_ | 1819009997359546368 |
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| author | Wen-Ning Xu Run-Ze Yang Huo-Liang Zheng Lei-Sheng Jiang Sheng-Dan Jiang |
| author_facet | Wen-Ning Xu Run-Ze Yang Huo-Liang Zheng Lei-Sheng Jiang Sheng-Dan Jiang |
| author_sort | Wen-Ning Xu |
| collection | DOAJ |
| description | Osteosarcoma (OS) accounts for a large proportion of the types of bone tumors that are newly diagnosed, and is a relatively common bone tumor. However, there are still no effective treatments for this affliction. One interesting avenue is related to the mitochondrial NDUFA4L2 protein, which is encoded by the nuclear gene and is known to be a critical mediator in the regulation of cell survival. Thus, in this study, we aimed to investigate the effect of NDUFA4L2 upon the metastasis and epithelial–mesenchymal transition of OS. We found that NDUFA4L2 protein expression was upregulated in hypoxic conditions. We also used 2-ME and DMOG, which are HIF-1α inhibitors and agonists, respectively, to assess the effects related to decreasing or increasing HIF-1α expression. 2-ME caused a significant decrease of NDUFA4L2 expression and DMOG had the opposite effect. It was obvious that down-regulation of NDUFA4L2 had a direct interaction with the apoptosis of OS cells. Western blotting, wound healing analyses, Transwell invasion assays, and colony formation assays all indicated and supported the conclusion that NDUFA4L2 promoted OS cell migration, invasion, proliferation, and the epithelial–mesenchymal transition. During experiments, we incidentally discovered that autophagy and the ROS inhibitor could be used to facilitate the rescuing of tumor cells whose NDUFA4L2 was knocked down. Our findings will help to further elucidate the dynamics underlying the mechanism of OS cells and have provided a novel therapeutic target for the treatment of OS. |
| first_indexed | 2024-12-21T01:05:15Z |
| format | Article |
| id | doaj.art-1459a393737c487a8b1f8a5fcad2503f |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T01:05:15Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-1459a393737c487a8b1f8a5fcad2503f2022-12-21T19:21:03ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-11-01810.3389/fcell.2020.515051515051NDUFA4L2 Regulated by HIF-1α Promotes Metastasis and Epithelial–Mesenchymal Transition of Osteosarcoma Cells Through Inhibiting ROS ProductionWen-Ning XuRun-Ze YangHuo-Liang ZhengLei-Sheng JiangSheng-Dan JiangOsteosarcoma (OS) accounts for a large proportion of the types of bone tumors that are newly diagnosed, and is a relatively common bone tumor. However, there are still no effective treatments for this affliction. One interesting avenue is related to the mitochondrial NDUFA4L2 protein, which is encoded by the nuclear gene and is known to be a critical mediator in the regulation of cell survival. Thus, in this study, we aimed to investigate the effect of NDUFA4L2 upon the metastasis and epithelial–mesenchymal transition of OS. We found that NDUFA4L2 protein expression was upregulated in hypoxic conditions. We also used 2-ME and DMOG, which are HIF-1α inhibitors and agonists, respectively, to assess the effects related to decreasing or increasing HIF-1α expression. 2-ME caused a significant decrease of NDUFA4L2 expression and DMOG had the opposite effect. It was obvious that down-regulation of NDUFA4L2 had a direct interaction with the apoptosis of OS cells. Western blotting, wound healing analyses, Transwell invasion assays, and colony formation assays all indicated and supported the conclusion that NDUFA4L2 promoted OS cell migration, invasion, proliferation, and the epithelial–mesenchymal transition. During experiments, we incidentally discovered that autophagy and the ROS inhibitor could be used to facilitate the rescuing of tumor cells whose NDUFA4L2 was knocked down. Our findings will help to further elucidate the dynamics underlying the mechanism of OS cells and have provided a novel therapeutic target for the treatment of OS.https://www.frontiersin.org/articles/10.3389/fcell.2020.515051/fullHIF-1ahypoxiaosteosarcomametastasesNDUFA4L2 |
| spellingShingle | Wen-Ning Xu Run-Ze Yang Huo-Liang Zheng Lei-Sheng Jiang Sheng-Dan Jiang NDUFA4L2 Regulated by HIF-1α Promotes Metastasis and Epithelial–Mesenchymal Transition of Osteosarcoma Cells Through Inhibiting ROS Production Frontiers in Cell and Developmental Biology HIF-1a hypoxia osteosarcoma metastases NDUFA4L2 |
| title | NDUFA4L2 Regulated by HIF-1α Promotes Metastasis and Epithelial–Mesenchymal Transition of Osteosarcoma Cells Through Inhibiting ROS Production |
| title_full | NDUFA4L2 Regulated by HIF-1α Promotes Metastasis and Epithelial–Mesenchymal Transition of Osteosarcoma Cells Through Inhibiting ROS Production |
| title_fullStr | NDUFA4L2 Regulated by HIF-1α Promotes Metastasis and Epithelial–Mesenchymal Transition of Osteosarcoma Cells Through Inhibiting ROS Production |
| title_full_unstemmed | NDUFA4L2 Regulated by HIF-1α Promotes Metastasis and Epithelial–Mesenchymal Transition of Osteosarcoma Cells Through Inhibiting ROS Production |
| title_short | NDUFA4L2 Regulated by HIF-1α Promotes Metastasis and Epithelial–Mesenchymal Transition of Osteosarcoma Cells Through Inhibiting ROS Production |
| title_sort | ndufa4l2 regulated by hif 1α promotes metastasis and epithelial mesenchymal transition of osteosarcoma cells through inhibiting ros production |
| topic | HIF-1a hypoxia osteosarcoma metastases NDUFA4L2 |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2020.515051/full |
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