PAGE4 promotes prostate cancer cells survive under oxidative stress through modulating MAPK/JNK/ERK pathway
Abstract Background Prostate cancer (PCa) is one of the most common cancers in male worldwide. Oxidative stress has been recognized as one of the driving signals pathologically linked to PCa progression. Nevertheless, the association of oxidative stress with PCa progression remains unclear. Methods...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-019-1032-3 |
| _version_ | 1819237139875889152 |
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| author | Chengcheng Lv Shui Fu Qingzhuo Dong Zi Yu Gejun Zhang Chuize Kong Cheng Fu Yu Zeng |
| author_facet | Chengcheng Lv Shui Fu Qingzhuo Dong Zi Yu Gejun Zhang Chuize Kong Cheng Fu Yu Zeng |
| author_sort | Chengcheng Lv |
| collection | DOAJ |
| description | Abstract Background Prostate cancer (PCa) is one of the most common cancers in male worldwide. Oxidative stress has been recognized as one of the driving signals pathologically linked to PCa progression. Nevertheless, the association of oxidative stress with PCa progression remains unclear. Methods Western blot, q-RT-PCR and bioinformatics analyses were used to examine PAGE4 expression. Comet assay and Annexin V/ PI dual staining assay were performed to investigate DNA damage and cell death under oxidative stress. Mouse xenograft model of PCa cells was established to verify the role of PAGE4 in vivo. Transcriptomic analysis was performed to investigate the underlying mechanism for the function of PAGE4 under oxidative stress. Western blot assay was conducted to determine the status of MAPK pathway. Immunohistochemistry was used to identify protein expression of PAGE4 in tumor tissues. Results In this study, we found that PAGE4 expression was increased in PCa cells under oxidative stress condition. PAGE4 overexpression protected PCa cells from oxidative stress-inducing cell death by reducing DNA damage. PAGE4 overexpression promoted PCa cells growth in vivo. Mechanistically, PAGE4 promoted the survival of prostate cancer cells through regulating MAPK pathway which reflected in decreasing the phosphorylation of MAP2K4, JNK and c-JUN but increasing phosphorylation of ERK1/2. Conclusion Our findings indicate that PAGE4 protects PCa cells from DNA damage and apoptosis under oxidative stress by modulating MAPK signalling pathway. PAGE4 expression may serve as a prognostic biomarker for clinical applications. |
| first_indexed | 2024-12-23T13:15:35Z |
| format | Article |
| id | doaj.art-1636274b0a2a4411a4dbe9c22239f0d7 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-23T13:15:35Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-1636274b0a2a4411a4dbe9c22239f0d72022-12-21T17:45:36ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-01-0138111510.1186/s13046-019-1032-3PAGE4 promotes prostate cancer cells survive under oxidative stress through modulating MAPK/JNK/ERK pathwayChengcheng Lv0Shui Fu1Qingzhuo Dong2Zi Yu3Gejun Zhang4Chuize Kong5Cheng Fu6Yu Zeng7Department of Urology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and InstituteDepartment of Urology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and InstituteDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and InstituteDepartment of Urology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and InstituteAbstract Background Prostate cancer (PCa) is one of the most common cancers in male worldwide. Oxidative stress has been recognized as one of the driving signals pathologically linked to PCa progression. Nevertheless, the association of oxidative stress with PCa progression remains unclear. Methods Western blot, q-RT-PCR and bioinformatics analyses were used to examine PAGE4 expression. Comet assay and Annexin V/ PI dual staining assay were performed to investigate DNA damage and cell death under oxidative stress. Mouse xenograft model of PCa cells was established to verify the role of PAGE4 in vivo. Transcriptomic analysis was performed to investigate the underlying mechanism for the function of PAGE4 under oxidative stress. Western blot assay was conducted to determine the status of MAPK pathway. Immunohistochemistry was used to identify protein expression of PAGE4 in tumor tissues. Results In this study, we found that PAGE4 expression was increased in PCa cells under oxidative stress condition. PAGE4 overexpression protected PCa cells from oxidative stress-inducing cell death by reducing DNA damage. PAGE4 overexpression promoted PCa cells growth in vivo. Mechanistically, PAGE4 promoted the survival of prostate cancer cells through regulating MAPK pathway which reflected in decreasing the phosphorylation of MAP2K4, JNK and c-JUN but increasing phosphorylation of ERK1/2. Conclusion Our findings indicate that PAGE4 protects PCa cells from DNA damage and apoptosis under oxidative stress by modulating MAPK signalling pathway. PAGE4 expression may serve as a prognostic biomarker for clinical applications.http://link.springer.com/article/10.1186/s13046-019-1032-3PAGE4Oxidative stressProstate CancerMAPKERK |
| spellingShingle | Chengcheng Lv Shui Fu Qingzhuo Dong Zi Yu Gejun Zhang Chuize Kong Cheng Fu Yu Zeng PAGE4 promotes prostate cancer cells survive under oxidative stress through modulating MAPK/JNK/ERK pathway Journal of Experimental & Clinical Cancer Research PAGE4 Oxidative stress Prostate Cancer MAPK ERK |
| title | PAGE4 promotes prostate cancer cells survive under oxidative stress through modulating MAPK/JNK/ERK pathway |
| title_full | PAGE4 promotes prostate cancer cells survive under oxidative stress through modulating MAPK/JNK/ERK pathway |
| title_fullStr | PAGE4 promotes prostate cancer cells survive under oxidative stress through modulating MAPK/JNK/ERK pathway |
| title_full_unstemmed | PAGE4 promotes prostate cancer cells survive under oxidative stress through modulating MAPK/JNK/ERK pathway |
| title_short | PAGE4 promotes prostate cancer cells survive under oxidative stress through modulating MAPK/JNK/ERK pathway |
| title_sort | page4 promotes prostate cancer cells survive under oxidative stress through modulating mapk jnk erk pathway |
| topic | PAGE4 Oxidative stress Prostate Cancer MAPK ERK |
| url | http://link.springer.com/article/10.1186/s13046-019-1032-3 |
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