Identification of mitochondrial carrier homolog 2 as an important therapeutic target of castration-resistant prostate cancer
Abstract We here investigate the expression of the mitochondrial carrier homolog 2 (MTCH2) and its potential function in castration-resistant prostate cancer (CRPC). Bioinformatic analyses reveal that MTCH2 overexpression is associated with critical clinical parameters of prostate cancer. Single-cel...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-02-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07406-5 |
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| _version_ | 1823861562549469184 |
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| author | Yankui Liu Anjie Chen Yufan Wu Jiang Ni Rong Wang Yong Mao Ning Sun Yuanyuan Mi |
| author_facet | Yankui Liu Anjie Chen Yufan Wu Jiang Ni Rong Wang Yong Mao Ning Sun Yuanyuan Mi |
| author_sort | Yankui Liu |
| collection | DOAJ |
| description | Abstract We here investigate the expression of the mitochondrial carrier homolog 2 (MTCH2) and its potential function in castration-resistant prostate cancer (CRPC). Bioinformatic analyses reveal that MTCH2 overexpression is associated with critical clinical parameters of prostate cancer. Single-cell sequencing data indicate elevated MTCH2 expression in the prostate cancer epithelium. MTCH2 is also upregulated in locally treated CRPC tissue and various primary human CRPC cells. Using genetic silencing via shRNA and knockout (KO) through the CRISPR-sgRNA approach, we showed that the depletion of MTCH2 impaired mitochondrial function, resulting in a reduced oxygen consumption rate, diminished complex I activity, and decreased ATP levels, mitochondrial depolarization, and increased reactive oxygen species production in primary CRPC cells. The silencing or KO of MTCH2 significantly inhibited cell viability, proliferation, and migration, together with a marked increase in apoptosis in the primary CRPC cells. In contrast, ectopic expression of MTCH2 provided CRPC cells with pro-tumorigenic properties, enhancing ATP production and promoting cell proliferation and migration. MTCH2 silencing also markedly inhibited the growth of subcutaneous xenografts of the primary CRPC cells in nude mice. The MTCH2-silenced xenografts exhibited increased apoptosis, elevated lipid peroxidation, and decreased ATP levels. These results provide new insights into the role of MTCH2 in supporting mitochondrial function and CRPC progression. |
| format | Article |
| id | doaj-art-60f3eea750bd46d6a8c48169bd915719 |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-60f3eea750bd46d6a8c48169bd9157192025-02-09T12:56:44ZengNature Publishing GroupCell Death and Disease2041-48892025-02-0116111410.1038/s41419-025-07406-5Identification of mitochondrial carrier homolog 2 as an important therapeutic target of castration-resistant prostate cancerYankui Liu0Anjie Chen1Yufan Wu2Jiang Ni3Rong Wang4Yong Mao5Ning Sun6Yuanyuan Mi7Department of Pathology, Affiliated Hospital of Jiangnan UniversityWuxi School of Medicine, Jiangnan UniversityDepartment of Urology, Kunshan Hospital of Traditional Chinese MedicineDepartment of Pharmacy, Affiliated Hospital of Jiangnan UniversityWuxi School of Medicine, Jiangnan UniversityDepartment of Oncology, Affiliated Hospital of Jiangnan UniversityWuxi School of Medicine, Jiangnan UniversityDepartment of Urology, Affiliated Hospital of Jiangnan UniversityAbstract We here investigate the expression of the mitochondrial carrier homolog 2 (MTCH2) and its potential function in castration-resistant prostate cancer (CRPC). Bioinformatic analyses reveal that MTCH2 overexpression is associated with critical clinical parameters of prostate cancer. Single-cell sequencing data indicate elevated MTCH2 expression in the prostate cancer epithelium. MTCH2 is also upregulated in locally treated CRPC tissue and various primary human CRPC cells. Using genetic silencing via shRNA and knockout (KO) through the CRISPR-sgRNA approach, we showed that the depletion of MTCH2 impaired mitochondrial function, resulting in a reduced oxygen consumption rate, diminished complex I activity, and decreased ATP levels, mitochondrial depolarization, and increased reactive oxygen species production in primary CRPC cells. The silencing or KO of MTCH2 significantly inhibited cell viability, proliferation, and migration, together with a marked increase in apoptosis in the primary CRPC cells. In contrast, ectopic expression of MTCH2 provided CRPC cells with pro-tumorigenic properties, enhancing ATP production and promoting cell proliferation and migration. MTCH2 silencing also markedly inhibited the growth of subcutaneous xenografts of the primary CRPC cells in nude mice. The MTCH2-silenced xenografts exhibited increased apoptosis, elevated lipid peroxidation, and decreased ATP levels. These results provide new insights into the role of MTCH2 in supporting mitochondrial function and CRPC progression.https://doi.org/10.1038/s41419-025-07406-5 |
| spellingShingle | Yankui Liu Anjie Chen Yufan Wu Jiang Ni Rong Wang Yong Mao Ning Sun Yuanyuan Mi Identification of mitochondrial carrier homolog 2 as an important therapeutic target of castration-resistant prostate cancer Cell Death and Disease |
| title | Identification of mitochondrial carrier homolog 2 as an important therapeutic target of castration-resistant prostate cancer |
| title_full | Identification of mitochondrial carrier homolog 2 as an important therapeutic target of castration-resistant prostate cancer |
| title_fullStr | Identification of mitochondrial carrier homolog 2 as an important therapeutic target of castration-resistant prostate cancer |
| title_full_unstemmed | Identification of mitochondrial carrier homolog 2 as an important therapeutic target of castration-resistant prostate cancer |
| title_short | Identification of mitochondrial carrier homolog 2 as an important therapeutic target of castration-resistant prostate cancer |
| title_sort | identification of mitochondrial carrier homolog 2 as an important therapeutic target of castration resistant prostate cancer |
| url | https://doi.org/10.1038/s41419-025-07406-5 |
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