KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer
PARP inhibitors (PARPi) are currently used as first-line therapy for advanced and recurrent ovarian cancer, but the clinical efficacy is limited by drug resistance. We aimed to investigate the role of KIAA1529 in PARPi resistance in ovarian cancer. The expression of KIAA1529 was determined in ovaria...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523322001565 |
| _version_ | 1798040474462715904 |
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| author | Yuan Qiao Xuechen Yu Bo Zhou Kai Zhang Juyuan Huang Jing Liao |
| author_facet | Yuan Qiao Xuechen Yu Bo Zhou Kai Zhang Juyuan Huang Jing Liao |
| author_sort | Yuan Qiao |
| collection | DOAJ |
| description | PARP inhibitors (PARPi) are currently used as first-line therapy for advanced and recurrent ovarian cancer, but the clinical efficacy is limited by drug resistance. We aimed to investigate the role of KIAA1529 in PARPi resistance in ovarian cancer. The expression of KIAA1529 was determined in ovarian cancer cells using qRT‒PCR and western blotting. Immunohistochemistry was used to examine the expression of KIAA1529 in primary ovarian cancer and recurrent ovarian cancer tissues. The effects of KIAA1529 on PARPi resistance were evaluated by knocking down KIAA1529 expression in ovarian cancer cells and assessing cell viability by CCK8 assays, apoptosis by flow cytometry, and homologous recombination (HR) repair by immunofluorescence analysis. The interaction between KIAA1529 and RAD51 was examined by western blotting. KIAA1529 was confirmed to be expressed in all ovarian cancer cell lines, and high expression of KIAA1529 was observed in recurrent ovarian cancer tissues. Inhibiting KIAA1529 expression increased the sensitivity of ovarian cancer cells to PARPi treatment. Furthermore, KIAA1529 increased the expression of the downstream effector RAD51 via Aurora-A, and HR was restored in ovarian cancer cells. This study demonstrates that KIAA1529 regulates RAD51 expression through Aurora-A to restore HR, which confers resistance to PARPi in ovarian cancer cells. These findings could provide a novel therapeutic target to overcome PARPi resistance in ovarian cancer. |
| first_indexed | 2024-04-11T22:08:07Z |
| format | Article |
| id | doaj.art-81fd0bb26e704d0ca75cf532b99e2a90 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-04-11T22:08:07Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-81fd0bb26e704d0ca75cf532b99e2a902022-12-22T04:00:38ZengElsevierTranslational Oncology1936-52332022-10-0124101497KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancerYuan Qiao0Xuechen Yu1Bo Zhou2Kai Zhang3Juyuan Huang4Jing Liao5Department of Gynaecology and Obstetrics, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, ChinaDepartment of Gynaecology and Obstetrics, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, ChinaDepartment of Gynaecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, ChinaDepartment of Gynaecology and Obstetrics, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, ChinaDepartment of Gynaecology and Obstetrics, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, ChinaDepartment of Gynaecology and Obstetrics, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China; Corresponding author: Jing Liao, Department of Gynaecology and Obstetrics, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China.PARP inhibitors (PARPi) are currently used as first-line therapy for advanced and recurrent ovarian cancer, but the clinical efficacy is limited by drug resistance. We aimed to investigate the role of KIAA1529 in PARPi resistance in ovarian cancer. The expression of KIAA1529 was determined in ovarian cancer cells using qRT‒PCR and western blotting. Immunohistochemistry was used to examine the expression of KIAA1529 in primary ovarian cancer and recurrent ovarian cancer tissues. The effects of KIAA1529 on PARPi resistance were evaluated by knocking down KIAA1529 expression in ovarian cancer cells and assessing cell viability by CCK8 assays, apoptosis by flow cytometry, and homologous recombination (HR) repair by immunofluorescence analysis. The interaction between KIAA1529 and RAD51 was examined by western blotting. KIAA1529 was confirmed to be expressed in all ovarian cancer cell lines, and high expression of KIAA1529 was observed in recurrent ovarian cancer tissues. Inhibiting KIAA1529 expression increased the sensitivity of ovarian cancer cells to PARPi treatment. Furthermore, KIAA1529 increased the expression of the downstream effector RAD51 via Aurora-A, and HR was restored in ovarian cancer cells. This study demonstrates that KIAA1529 regulates RAD51 expression through Aurora-A to restore HR, which confers resistance to PARPi in ovarian cancer cells. These findings could provide a novel therapeutic target to overcome PARPi resistance in ovarian cancer.http://www.sciencedirect.com/science/article/pii/S1936523322001565KIAA1529RAD51PARP inhibitorsResistanceOvarian cancer |
| spellingShingle | Yuan Qiao Xuechen Yu Bo Zhou Kai Zhang Juyuan Huang Jing Liao KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer Translational Oncology KIAA1529 RAD51 PARP inhibitors Resistance Ovarian cancer |
| title | KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer |
| title_full | KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer |
| title_fullStr | KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer |
| title_full_unstemmed | KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer |
| title_short | KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer |
| title_sort | kiaa1529 regulates rad51 expression to confer parp inhibitors resistance in ovarian cancer |
| topic | KIAA1529 RAD51 PARP inhibitors Resistance Ovarian cancer |
| url | http://www.sciencedirect.com/science/article/pii/S1936523322001565 |
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