FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A
Abstract Background Docetaxel resistance affects prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. Transcription factor Forkhead box M1 (FOXM1), which participates in cell proliferation and cell cycle progression, has been reported to affect the sensitivity of chemo...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-11-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01631-y |
| _version_ | 1818261379126132736 |
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| author | Hongbo Yu Zheng Xu Maomao Guo Weiwan Wang Weican Zhang Sudong Liang Zhibin Xu Jun Ye Gangyi Zhu Chenyang Zhang Jianzhong Lin |
| author_facet | Hongbo Yu Zheng Xu Maomao Guo Weiwan Wang Weican Zhang Sudong Liang Zhibin Xu Jun Ye Gangyi Zhu Chenyang Zhang Jianzhong Lin |
| author_sort | Hongbo Yu |
| collection | DOAJ |
| description | Abstract Background Docetaxel resistance affects prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. Transcription factor Forkhead box M1 (FOXM1), which participates in cell proliferation and cell cycle progression, has been reported to affect the sensitivity of chemotherapy. This study explores the role of FOXM1 in PCa docetaxel resistance and its association with kinesin family member 20 A (KIF20A), which is known to promote therapeutic resistance in some cancers. Methods We monitored cell growth using MTT and colony formation assays, and cell apoptosis and cell cycle progression using flow cytometry. Wound-healing and transwell assays were used to detect cell invasion and migration. mRNA and protein expression were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. We monitored FOXM1 binding to the KIF20A promoter using a ChIP assay. Tumorigenicity in nude mice was used to assess in vivo tumorigenicity. Results FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, suppressing cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). Exogenous FOXM1 overexpression was found in their parental cells. Specific FOXM1 inhibitor thiostrepton significantly weakened docetaxel resistance in vitro and in vivo. We also found that FOXM1 and KIF20A exhibited consistent and highly correlated overexpression in PCa cells and tissues. FOXM1 also regulated KIF20A expression at the transcriptional level by acting directly on a Forkhead response element (FHRE) in its promoter. KIF20A overexpression could partially reverse the effect on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP) of FOXM1 depletion. Conclusions Our findings indicate that highly expressed FOXM1 may help promote docetaxel resistance by inducing KIF20A expression, providing insight into novel chemotherapeutic strategies for combatting PCa docetaxel resistance. |
| first_indexed | 2024-12-12T18:46:17Z |
| format | Article |
| id | doaj.art-8a595272e6fc44698b0bbb1781ca8cd3 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-12T18:46:17Z |
| publishDate | 2020-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-8a595272e6fc44698b0bbb1781ca8cd32022-12-22T00:15:31ZengBMCCancer Cell International1475-28672020-11-0120111210.1186/s12935-020-01631-yFOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20AHongbo Yu0Zheng Xu1Maomao Guo2Weiwan Wang3Weican Zhang4Sudong Liang5Zhibin Xu6Jun Ye7Gangyi Zhu8Chenyang Zhang9Jianzhong Lin10Department of Urology, BenQ Medical Center, Nanjing Medical UniversityNanjing First Hospital, Nanjing Medical UniversityDepartment of Urology, Hospital Affiliated 5 to Nantong University (Taizhou People’s Hospital)Central Laboratory, BenQ Medical Center, Nanjing Medical UniversityThe First Clinical Medical College, Nanjing Medical UniversityDepartment of Urology, Hospital Affiliated 5 to Nantong University (Taizhou People’s Hospital)Central Laboratory, BenQ Medical Center, Nanjing Medical UniversityCentral Laboratory, Hospital Affiliated 5 to Nantong University (Taizhou People’s Hospital)Central Laboratory, BenQ Medical Center, Nanjing Medical UniversityCentral Laboratory, BenQ Medical Center, Nanjing Medical UniversityDepartment of Urology, Hospital Affiliated 5 to Nantong University (Taizhou People’s Hospital)Abstract Background Docetaxel resistance affects prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. Transcription factor Forkhead box M1 (FOXM1), which participates in cell proliferation and cell cycle progression, has been reported to affect the sensitivity of chemotherapy. This study explores the role of FOXM1 in PCa docetaxel resistance and its association with kinesin family member 20 A (KIF20A), which is known to promote therapeutic resistance in some cancers. Methods We monitored cell growth using MTT and colony formation assays, and cell apoptosis and cell cycle progression using flow cytometry. Wound-healing and transwell assays were used to detect cell invasion and migration. mRNA and protein expression were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. We monitored FOXM1 binding to the KIF20A promoter using a ChIP assay. Tumorigenicity in nude mice was used to assess in vivo tumorigenicity. Results FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, suppressing cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). Exogenous FOXM1 overexpression was found in their parental cells. Specific FOXM1 inhibitor thiostrepton significantly weakened docetaxel resistance in vitro and in vivo. We also found that FOXM1 and KIF20A exhibited consistent and highly correlated overexpression in PCa cells and tissues. FOXM1 also regulated KIF20A expression at the transcriptional level by acting directly on a Forkhead response element (FHRE) in its promoter. KIF20A overexpression could partially reverse the effect on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP) of FOXM1 depletion. Conclusions Our findings indicate that highly expressed FOXM1 may help promote docetaxel resistance by inducing KIF20A expression, providing insight into novel chemotherapeutic strategies for combatting PCa docetaxel resistance.http://link.springer.com/article/10.1186/s12935-020-01631-yFOXM1Prostate cancerDocetaxelResistanceKIF20A |
| spellingShingle | Hongbo Yu Zheng Xu Maomao Guo Weiwan Wang Weican Zhang Sudong Liang Zhibin Xu Jun Ye Gangyi Zhu Chenyang Zhang Jianzhong Lin FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A Cancer Cell International FOXM1 Prostate cancer Docetaxel Resistance KIF20A |
| title | FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A |
| title_full | FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A |
| title_fullStr | FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A |
| title_full_unstemmed | FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A |
| title_short | FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A |
| title_sort | foxm1 modulates docetaxel resistance in prostate cancer by regulating kif20a |
| topic | FOXM1 Prostate cancer Docetaxel Resistance KIF20A |
| url | http://link.springer.com/article/10.1186/s12935-020-01631-y |
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