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HOXC13-driven TIMM13 overexpression promotes osteosarcoma cell growth
TIMM13 (translocase of inner mitochondrial membrane 13) located at the mitochondrial intermembrane space is vital for the integrity and function of mitochondria. We found that the mitochondrial protein TIMM13 is upregulated in human OS tissues and cells. In patient-derived primary OS cells and estab...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10322838/ https://www.ncbi.nlm.nih.gov/pubmed/37407582 http://dx.doi.org/10.1038/s41419-023-05910-0 |
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author | Han, Qicai Yan, Penghui Song, Ruipeng Liu, Feifei Tian, Qing |
author_facet | Han, Qicai Yan, Penghui Song, Ruipeng Liu, Feifei Tian, Qing |
author_sort | Han, Qicai |
collection | PubMed |
description | TIMM13 (translocase of inner mitochondrial membrane 13) located at the mitochondrial intermembrane space is vital for the integrity and function of mitochondria. We found that the mitochondrial protein TIMM13 is upregulated in human OS tissues and cells. In patient-derived primary OS cells and established cell lines, TIMM13 shRNA or knockout provoked mitochondrial dysfunction, causing mitochondrial depolarization, reactive oxygen species production, and oxidative injury, as well as lipid peroxidation, DNA damage, and ATP depletion. Moreover, TIMM13 depletion provoked OS cell apoptosis and inhibited cell proliferation and migration. Conversely, ectopic TIMM13 overexpression increased ATP contents, enhancing OS cell proliferation and migration. Moreover, we discovered that Akt-mTOR activation was inhibited with TIMM13 depletion in primary OS cells. Further studies revealed that HOXC13 (Homeobox C13)-dependent TIMM13 transcription was significantly increased in OS tissues and cells. Whereas TIMM13 transcription and expression were decreased following HOXC13 silencing in primary OS cells. In vivo, TIMM13 KO potently inhibited OS xenograft growth in the proximal tibia of nude mice. TIMM13 KO also induced Akt-mTOR inactivation, ATP depletion, oxidative injury, and apoptosis in the in situ OS tumors. Together, upregulation of the mitochondrial protein TIMM13 is important for OS cell growth, representing a novel and promising therapeutic target. |
format | Online Article Text |
id | pubmed-10322838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-103228382023-07-07 HOXC13-driven TIMM13 overexpression promotes osteosarcoma cell growth Han, Qicai Yan, Penghui Song, Ruipeng Liu, Feifei Tian, Qing Cell Death Dis Article TIMM13 (translocase of inner mitochondrial membrane 13) located at the mitochondrial intermembrane space is vital for the integrity and function of mitochondria. We found that the mitochondrial protein TIMM13 is upregulated in human OS tissues and cells. In patient-derived primary OS cells and established cell lines, TIMM13 shRNA or knockout provoked mitochondrial dysfunction, causing mitochondrial depolarization, reactive oxygen species production, and oxidative injury, as well as lipid peroxidation, DNA damage, and ATP depletion. Moreover, TIMM13 depletion provoked OS cell apoptosis and inhibited cell proliferation and migration. Conversely, ectopic TIMM13 overexpression increased ATP contents, enhancing OS cell proliferation and migration. Moreover, we discovered that Akt-mTOR activation was inhibited with TIMM13 depletion in primary OS cells. Further studies revealed that HOXC13 (Homeobox C13)-dependent TIMM13 transcription was significantly increased in OS tissues and cells. Whereas TIMM13 transcription and expression were decreased following HOXC13 silencing in primary OS cells. In vivo, TIMM13 KO potently inhibited OS xenograft growth in the proximal tibia of nude mice. TIMM13 KO also induced Akt-mTOR inactivation, ATP depletion, oxidative injury, and apoptosis in the in situ OS tumors. Together, upregulation of the mitochondrial protein TIMM13 is important for OS cell growth, representing a novel and promising therapeutic target. Nature Publishing Group UK 2023-07-05 /pmc/articles/PMC10322838/ /pubmed/37407582 http://dx.doi.org/10.1038/s41419-023-05910-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Han, Qicai Yan, Penghui Song, Ruipeng Liu, Feifei Tian, Qing HOXC13-driven TIMM13 overexpression promotes osteosarcoma cell growth |
title | HOXC13-driven TIMM13 overexpression promotes osteosarcoma cell growth |
title_full | HOXC13-driven TIMM13 overexpression promotes osteosarcoma cell growth |
title_fullStr | HOXC13-driven TIMM13 overexpression promotes osteosarcoma cell growth |
title_full_unstemmed | HOXC13-driven TIMM13 overexpression promotes osteosarcoma cell growth |
title_short | HOXC13-driven TIMM13 overexpression promotes osteosarcoma cell growth |
title_sort | hoxc13-driven timm13 overexpression promotes osteosarcoma cell growth |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10322838/ https://www.ncbi.nlm.nih.gov/pubmed/37407582 http://dx.doi.org/10.1038/s41419-023-05910-0 |
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