A novel polypeptide encoded by circSPIRE1 promotes prostate cancer proliferation and migration by restraining the ubiquitin-dependent degradation of LRP5
Abstract Background Circular RNAs (circRNAs) are increasingly implicated in tumor progression, but the roles of protein-coding circRNAs remain largely unexplored. This study characterizes a novel circRNA-encoded protein, rtSPIRE1, and investigates its mechanistic role in prostate cancer proliferatio...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13046-025-03467-8 |
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| _version_ | 1849235696534945792 |
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| author | Jintao Hu Juanyi Shi Junjie Wang Yunfei Xiao Degeng Kong Mingchao Gao Tianlong Luo Shizhong Xu Zhihan Yuan Xinyi Ma Xueseng Dong Jingang Huang Cheng Liu Kewei Xu |
| author_facet | Jintao Hu Juanyi Shi Junjie Wang Yunfei Xiao Degeng Kong Mingchao Gao Tianlong Luo Shizhong Xu Zhihan Yuan Xinyi Ma Xueseng Dong Jingang Huang Cheng Liu Kewei Xu |
| author_sort | Jintao Hu |
| collection | DOAJ |
| description | Abstract Background Circular RNAs (circRNAs) are increasingly implicated in tumor progression, but the roles of protein-coding circRNAs remain largely unexplored. This study characterizes a novel circRNA-encoded protein, rtSPIRE1, and investigates its mechanistic role in prostate cancer proliferation and migration, as well as its diagnostic and therapeutic potential. Methods RNA microarray identified circSPIRE1 in prostate cancer tissues. The translation of rtSPIRE1 was confirmed by polysome profiling analysis, Western blotting, and mass spectrometry. Expression levels of circSPIRE1 and rtSPIRE1 were analyzed via qPCR, FISH, and immunohistochemistry. Gain- and loss-of-function assays were performed to evaluate their effects on cell proliferation and migration. Mechanistic studies were conducted using RNA pulldown, RIP, co-immunoprecipitation, and molecular docking. Results We identified rtSPIRE1, a novel protein encoded by circSPIRE1 through rolling circle translation, whose expression is regulated by hnRNPA1-mediated symmetric dimethylation. Both circSPIRE1 and rtSPIRE1 were significantly upregulated in prostate cancer tissues and cell lines, with higher expression levels correlating with worse prognosis. Mechanistically, rtSPIRE1 stabilized LRP5 by inhibiting its ubiquitination and degradation, leading to sustained activation of the PI3K/AKT signaling pathway, which ultimately promotes prostate cancer cell proliferation and migration. Conclusions Our findings identify rtSPIRE1 as a critical oncogenic protein encoded by circSPIRE1 through rolling circle translation, with its expression regulated by hnRNPA1-mediated symmetric dimethylation. Mechanistically, rtSPIRE1 promotes proliferation and migration by stabilizing LRP5 and activating the PI3K/AKT signaling pathway. Together, circSPIRE1 and rtSPIRE1 represent promising diagnostic biomarkers and therapeutic targets for prostate cancer. |
| format | Article |
| id | doaj-art-a4e2ca137ea34a0d98bd7913c7cec77d |
| institution | Kabale University |
| issn | 1756-9966 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj-art-a4e2ca137ea34a0d98bd7913c7cec77d2025-08-20T04:02:42ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662025-07-0144112210.1186/s13046-025-03467-8A novel polypeptide encoded by circSPIRE1 promotes prostate cancer proliferation and migration by restraining the ubiquitin-dependent degradation of LRP5Jintao Hu0Juanyi Shi1Junjie Wang2Yunfei Xiao3Degeng Kong4Mingchao Gao5Tianlong Luo6Shizhong Xu7Zhihan Yuan8Xinyi Ma9Xueseng Dong10Jingang Huang11Cheng Liu12Kewei Xu13Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversitySun Yat-sen University School of Medicine, Sun Yat-sen UniversityThe Vancouver Prostate Centre, Department of Urologic Sciences, Vancouver General Hospital, The University of British ColumbiaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityAbstract Background Circular RNAs (circRNAs) are increasingly implicated in tumor progression, but the roles of protein-coding circRNAs remain largely unexplored. This study characterizes a novel circRNA-encoded protein, rtSPIRE1, and investigates its mechanistic role in prostate cancer proliferation and migration, as well as its diagnostic and therapeutic potential. Methods RNA microarray identified circSPIRE1 in prostate cancer tissues. The translation of rtSPIRE1 was confirmed by polysome profiling analysis, Western blotting, and mass spectrometry. Expression levels of circSPIRE1 and rtSPIRE1 were analyzed via qPCR, FISH, and immunohistochemistry. Gain- and loss-of-function assays were performed to evaluate their effects on cell proliferation and migration. Mechanistic studies were conducted using RNA pulldown, RIP, co-immunoprecipitation, and molecular docking. Results We identified rtSPIRE1, a novel protein encoded by circSPIRE1 through rolling circle translation, whose expression is regulated by hnRNPA1-mediated symmetric dimethylation. Both circSPIRE1 and rtSPIRE1 were significantly upregulated in prostate cancer tissues and cell lines, with higher expression levels correlating with worse prognosis. Mechanistically, rtSPIRE1 stabilized LRP5 by inhibiting its ubiquitination and degradation, leading to sustained activation of the PI3K/AKT signaling pathway, which ultimately promotes prostate cancer cell proliferation and migration. Conclusions Our findings identify rtSPIRE1 as a critical oncogenic protein encoded by circSPIRE1 through rolling circle translation, with its expression regulated by hnRNPA1-mediated symmetric dimethylation. Mechanistically, rtSPIRE1 promotes proliferation and migration by stabilizing LRP5 and activating the PI3K/AKT signaling pathway. Together, circSPIRE1 and rtSPIRE1 represent promising diagnostic biomarkers and therapeutic targets for prostate cancer.https://doi.org/10.1186/s13046-025-03467-8circSPIRE1Rolling circle translationPeptidehnRNPA1ProliferationMigration |
| spellingShingle | Jintao Hu Juanyi Shi Junjie Wang Yunfei Xiao Degeng Kong Mingchao Gao Tianlong Luo Shizhong Xu Zhihan Yuan Xinyi Ma Xueseng Dong Jingang Huang Cheng Liu Kewei Xu A novel polypeptide encoded by circSPIRE1 promotes prostate cancer proliferation and migration by restraining the ubiquitin-dependent degradation of LRP5 Journal of Experimental & Clinical Cancer Research circSPIRE1 Rolling circle translation Peptide hnRNPA1 Proliferation Migration |
| title | A novel polypeptide encoded by circSPIRE1 promotes prostate cancer proliferation and migration by restraining the ubiquitin-dependent degradation of LRP5 |
| title_full | A novel polypeptide encoded by circSPIRE1 promotes prostate cancer proliferation and migration by restraining the ubiquitin-dependent degradation of LRP5 |
| title_fullStr | A novel polypeptide encoded by circSPIRE1 promotes prostate cancer proliferation and migration by restraining the ubiquitin-dependent degradation of LRP5 |
| title_full_unstemmed | A novel polypeptide encoded by circSPIRE1 promotes prostate cancer proliferation and migration by restraining the ubiquitin-dependent degradation of LRP5 |
| title_short | A novel polypeptide encoded by circSPIRE1 promotes prostate cancer proliferation and migration by restraining the ubiquitin-dependent degradation of LRP5 |
| title_sort | novel polypeptide encoded by circspire1 promotes prostate cancer proliferation and migration by restraining the ubiquitin dependent degradation of lrp5 |
| topic | circSPIRE1 Rolling circle translation Peptide hnRNPA1 Proliferation Migration |
| url | https://doi.org/10.1186/s13046-025-03467-8 |
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