CRAT downregulation promotes ovarian cancer progression by facilitating mitochondrial metabolism through decreasing the acetylation of PGC-1α
Abstract Mitochondrial dysfunctions are closely associated with different types of disease, including cancer. Carnitine acetyltransferase (CRAT) is a mitochondrial-localized enzyme catalyzing the reversible transfer of acyl groups from an acyl-CoA thioester to carnitine and regulates the ratio of ac...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-01-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02294-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832595008312573952 |
|---|---|
| author | Zhen Zhang Shuhua Zhao Xiaohui Lv Yan Gao Qian Guo Yanjie Ren Yuanyuan He Yihua Jin Hong Yang Shujuan Liu Xiaohong Zhang |
| author_facet | Zhen Zhang Shuhua Zhao Xiaohui Lv Yan Gao Qian Guo Yanjie Ren Yuanyuan He Yihua Jin Hong Yang Shujuan Liu Xiaohong Zhang |
| author_sort | Zhen Zhang |
| collection | DOAJ |
| description | Abstract Mitochondrial dysfunctions are closely associated with different types of disease, including cancer. Carnitine acetyltransferase (CRAT) is a mitochondrial-localized enzyme catalyzing the reversible transfer of acyl groups from an acyl-CoA thioester to carnitine and regulates the ratio of acyl-CoA/CoA. Our bioinformatics analysis using public database revealed a significant decrease of CRAT expression in ovarian cancer (OC). However, the functions of CRAT have rarely been investigated in human cancers, especially in OC. Here, we found a frequent down-regulation of CRAT in OC, which is mainly caused by up-regulation of miR-132-5p. Downregulation of CRAT was significantly associated with shorter survival time for patients with OC. Forced expression of CRAT suppressed OC growth and metastasis by inducing cell cycle arrest and epithelial to mesenchymal transition (EMT). By contrast, CRAT knockdown promoted OC growth and metastasis. Mechanistically, we found that CRAT downregulation promoted OC growth and metastasis by increasing mitochondrial biogenesis to facilitate mitochondrial metabolism through reducing the acetylation of peroxisome proliferator-activated receptor-γ coactivator (PGC-1α). In summary, CRAT functions as a critical tumor suppressor in OC progression by enhancing PGC-1α-mediated mitochondrial biogenesis and metabolism, suggesting CRAT as a potential therapeutic target in treatment of OC. |
| format | Article |
| id | doaj-art-e3660fef5dc74bc185528d672620d39f |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-e3660fef5dc74bc185528d672620d39f2025-01-19T12:10:30ZengNature Publishing GroupCell Death Discovery2058-77162025-01-0111111410.1038/s41420-025-02294-2CRAT downregulation promotes ovarian cancer progression by facilitating mitochondrial metabolism through decreasing the acetylation of PGC-1αZhen Zhang0Shuhua Zhao1Xiaohui Lv2Yan Gao3Qian Guo4Yanjie Ren5Yuanyuan He6Yihua Jin7Hong Yang8Shujuan Liu9Xiaohong Zhang10Department of stomatology, Shaanxi Provincial People’s HospitalDepartment of Gynaecology and Obstetrics, Xijing Hospital, Air Force Medical UniversityDepartment of Gynaecology and Obstetrics, Xijing Hospital, Air Force Medical UniversityDepartment of Gynaecology and Obstetrics, Xijing Hospital, Air Force Medical UniversityDepartment of Gynaecology and Obstetrics, Xijing Hospital, Air Force Medical UniversityDepartment of Gynaecology and Obstetrics, Xijing Hospital, Air Force Medical UniversityDepartment of Gynaecology and Obstetrics, Xijing Hospital, Air Force Medical UniversityDepartment of Gynaecology and Obstetrics, Xijing Hospital, Air Force Medical UniversityDepartment of Gynaecology and Obstetrics, Xijing Hospital, Air Force Medical UniversityDepartment of Gynaecology and Obstetrics, Xijing Hospital, Air Force Medical UniversityDepartment of Gynaecology and Obstetrics, Xijing Hospital, Air Force Medical UniversityAbstract Mitochondrial dysfunctions are closely associated with different types of disease, including cancer. Carnitine acetyltransferase (CRAT) is a mitochondrial-localized enzyme catalyzing the reversible transfer of acyl groups from an acyl-CoA thioester to carnitine and regulates the ratio of acyl-CoA/CoA. Our bioinformatics analysis using public database revealed a significant decrease of CRAT expression in ovarian cancer (OC). However, the functions of CRAT have rarely been investigated in human cancers, especially in OC. Here, we found a frequent down-regulation of CRAT in OC, which is mainly caused by up-regulation of miR-132-5p. Downregulation of CRAT was significantly associated with shorter survival time for patients with OC. Forced expression of CRAT suppressed OC growth and metastasis by inducing cell cycle arrest and epithelial to mesenchymal transition (EMT). By contrast, CRAT knockdown promoted OC growth and metastasis. Mechanistically, we found that CRAT downregulation promoted OC growth and metastasis by increasing mitochondrial biogenesis to facilitate mitochondrial metabolism through reducing the acetylation of peroxisome proliferator-activated receptor-γ coactivator (PGC-1α). In summary, CRAT functions as a critical tumor suppressor in OC progression by enhancing PGC-1α-mediated mitochondrial biogenesis and metabolism, suggesting CRAT as a potential therapeutic target in treatment of OC.https://doi.org/10.1038/s41420-025-02294-2 |
| spellingShingle | Zhen Zhang Shuhua Zhao Xiaohui Lv Yan Gao Qian Guo Yanjie Ren Yuanyuan He Yihua Jin Hong Yang Shujuan Liu Xiaohong Zhang CRAT downregulation promotes ovarian cancer progression by facilitating mitochondrial metabolism through decreasing the acetylation of PGC-1α Cell Death Discovery |
| title | CRAT downregulation promotes ovarian cancer progression by facilitating mitochondrial metabolism through decreasing the acetylation of PGC-1α |
| title_full | CRAT downregulation promotes ovarian cancer progression by facilitating mitochondrial metabolism through decreasing the acetylation of PGC-1α |
| title_fullStr | CRAT downregulation promotes ovarian cancer progression by facilitating mitochondrial metabolism through decreasing the acetylation of PGC-1α |
| title_full_unstemmed | CRAT downregulation promotes ovarian cancer progression by facilitating mitochondrial metabolism through decreasing the acetylation of PGC-1α |
| title_short | CRAT downregulation promotes ovarian cancer progression by facilitating mitochondrial metabolism through decreasing the acetylation of PGC-1α |
| title_sort | crat downregulation promotes ovarian cancer progression by facilitating mitochondrial metabolism through decreasing the acetylation of pgc 1α |
| url | https://doi.org/10.1038/s41420-025-02294-2 |
| work_keys_str_mv | AT zhenzhang cratdownregulationpromotesovariancancerprogressionbyfacilitatingmitochondrialmetabolismthroughdecreasingtheacetylationofpgc1a AT shuhuazhao cratdownregulationpromotesovariancancerprogressionbyfacilitatingmitochondrialmetabolismthroughdecreasingtheacetylationofpgc1a AT xiaohuilv cratdownregulationpromotesovariancancerprogressionbyfacilitatingmitochondrialmetabolismthroughdecreasingtheacetylationofpgc1a AT yangao cratdownregulationpromotesovariancancerprogressionbyfacilitatingmitochondrialmetabolismthroughdecreasingtheacetylationofpgc1a AT qianguo cratdownregulationpromotesovariancancerprogressionbyfacilitatingmitochondrialmetabolismthroughdecreasingtheacetylationofpgc1a AT yanjieren cratdownregulationpromotesovariancancerprogressionbyfacilitatingmitochondrialmetabolismthroughdecreasingtheacetylationofpgc1a AT yuanyuanhe cratdownregulationpromotesovariancancerprogressionbyfacilitatingmitochondrialmetabolismthroughdecreasingtheacetylationofpgc1a AT yihuajin cratdownregulationpromotesovariancancerprogressionbyfacilitatingmitochondrialmetabolismthroughdecreasingtheacetylationofpgc1a AT hongyang cratdownregulationpromotesovariancancerprogressionbyfacilitatingmitochondrialmetabolismthroughdecreasingtheacetylationofpgc1a AT shujuanliu cratdownregulationpromotesovariancancerprogressionbyfacilitatingmitochondrialmetabolismthroughdecreasingtheacetylationofpgc1a AT xiaohongzhang cratdownregulationpromotesovariancancerprogressionbyfacilitatingmitochondrialmetabolismthroughdecreasingtheacetylationofpgc1a |