STUB1 suppresses paclitaxel resistance in ovarian cancer through mediating HOXB3 ubiquitination to inhibit PARK7 expression
Abstract Paclitaxel (PTX) is a first-line drug for ovarian cancer (OC) treatment. However, the regulatory mechanism of STUB1 on ferroptosis and PTX resistance in OC remains unclear. Genes and proteins levels were evaluated by RT-qPCR, western blot and IHC. Cell viability and proliferation were measu...
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| Format: | Article |
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Nature Portfolio
2024-11-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07127-z |
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| author | Laigang Zhao HanLin Yang Yuanmei Wang Shuang Yang Qisi Jiang Jun Tan Xing Zhao Dan Zi |
| author_facet | Laigang Zhao HanLin Yang Yuanmei Wang Shuang Yang Qisi Jiang Jun Tan Xing Zhao Dan Zi |
| author_sort | Laigang Zhao |
| collection | DOAJ |
| description | Abstract Paclitaxel (PTX) is a first-line drug for ovarian cancer (OC) treatment. However, the regulatory mechanism of STUB1 on ferroptosis and PTX resistance in OC remains unclear. Genes and proteins levels were evaluated by RT-qPCR, western blot and IHC. Cell viability and proliferation were measured by CCK-8 and clone formation. The changes of mitochondrial morphology were observed under a transmission electron microscope (TEM). Reactive oxygen species (ROS), iron, malondialdehyde (MDA) and glutathione (GSH) were measured using suitable kits. The interactions among STUB1, HOXB3 and PARK7 were validated using Co-IP, and dual luciferase reporter assay. Our study found that STUB1 was decreased and PARK7 was increased in tumor tissue, especially from chemotherapy resistant ovarian cancer tissue and resistant OC cells. STUB1 overexpression or PARK7 silencing suppressed cell growth and promoted ferroptosis in PTX-resistant OC cells, which was reversed by HOXB3 overexpression. Mechanistically, STUB1 mediated ubiquitination of HOXB3 to inhibit HOXB3 expression, and HOXB3 promoted the transcription of PARK7 by binding to the promoter region of PARK7. Furthermore, STUB1 overexpression or PARK7 silencing suppressed tumor formation in nude mice. In short, STUB1 promoted ferroptosis through regulating HOXB3/PARK7 axis, thereby suppressing chemotherapy resistance in OC. |
| format | Article |
| id | doaj-art-bc78538b816b4fc6b08ff2dc4e79a154 |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| series | Communications Biology |
| spelling | doaj-art-bc78538b816b4fc6b08ff2dc4e79a1542025-08-20T01:56:45ZengNature PortfolioCommunications Biology2399-36422024-11-017111310.1038/s42003-024-07127-zSTUB1 suppresses paclitaxel resistance in ovarian cancer through mediating HOXB3 ubiquitination to inhibit PARK7 expressionLaigang Zhao0HanLin Yang1Yuanmei Wang2Shuang Yang3Qisi Jiang4Jun Tan5Xing Zhao6Dan Zi7Department of gynecology and obstetrics, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical UniversityDepartment of Gynecology and obstetrics, Guizhou Provincial People’s HospitalDepartment of Gynecology and obstetrics, Guizhou Provincial People’s HospitalDepartment of oncology, Cangxi People’s HospitalSchool Hospital of Yangtze Normal UniversityKey Laboratory of Medical Molecular Biology, Guizhou Medical UniversityKey Laboratory of Adult Stem Cell Transformation Research, Chinese Academy of Medical Sciences/Stem Cell and Tissue Engineering Research Center, Guizhou Medical UniversityDepartment of Gynecology and obstetrics, Guizhou Provincial People’s HospitalAbstract Paclitaxel (PTX) is a first-line drug for ovarian cancer (OC) treatment. However, the regulatory mechanism of STUB1 on ferroptosis and PTX resistance in OC remains unclear. Genes and proteins levels were evaluated by RT-qPCR, western blot and IHC. Cell viability and proliferation were measured by CCK-8 and clone formation. The changes of mitochondrial morphology were observed under a transmission electron microscope (TEM). Reactive oxygen species (ROS), iron, malondialdehyde (MDA) and glutathione (GSH) were measured using suitable kits. The interactions among STUB1, HOXB3 and PARK7 were validated using Co-IP, and dual luciferase reporter assay. Our study found that STUB1 was decreased and PARK7 was increased in tumor tissue, especially from chemotherapy resistant ovarian cancer tissue and resistant OC cells. STUB1 overexpression or PARK7 silencing suppressed cell growth and promoted ferroptosis in PTX-resistant OC cells, which was reversed by HOXB3 overexpression. Mechanistically, STUB1 mediated ubiquitination of HOXB3 to inhibit HOXB3 expression, and HOXB3 promoted the transcription of PARK7 by binding to the promoter region of PARK7. Furthermore, STUB1 overexpression or PARK7 silencing suppressed tumor formation in nude mice. In short, STUB1 promoted ferroptosis through regulating HOXB3/PARK7 axis, thereby suppressing chemotherapy resistance in OC.https://doi.org/10.1038/s42003-024-07127-z |
| spellingShingle | Laigang Zhao HanLin Yang Yuanmei Wang Shuang Yang Qisi Jiang Jun Tan Xing Zhao Dan Zi STUB1 suppresses paclitaxel resistance in ovarian cancer through mediating HOXB3 ubiquitination to inhibit PARK7 expression Communications Biology |
| title | STUB1 suppresses paclitaxel resistance in ovarian cancer through mediating HOXB3 ubiquitination to inhibit PARK7 expression |
| title_full | STUB1 suppresses paclitaxel resistance in ovarian cancer through mediating HOXB3 ubiquitination to inhibit PARK7 expression |
| title_fullStr | STUB1 suppresses paclitaxel resistance in ovarian cancer through mediating HOXB3 ubiquitination to inhibit PARK7 expression |
| title_full_unstemmed | STUB1 suppresses paclitaxel resistance in ovarian cancer through mediating HOXB3 ubiquitination to inhibit PARK7 expression |
| title_short | STUB1 suppresses paclitaxel resistance in ovarian cancer through mediating HOXB3 ubiquitination to inhibit PARK7 expression |
| title_sort | stub1 suppresses paclitaxel resistance in ovarian cancer through mediating hoxb3 ubiquitination to inhibit park7 expression |
| url | https://doi.org/10.1038/s42003-024-07127-z |
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