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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13046-025-03467-8","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T03:52:30Z","timestamp":1753415550000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A novel polypeptide encoded by circSPIRE1 promotes prostate cancer proliferation and migration by restraining the ubiquitin-dependent degradation of LRP5"],"prefix":"10.1186","volume":"44","author":[{"given":"Jintao","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanyi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Degeng","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingchao","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianlong","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizhong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihan","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueseng","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"issue":"10437","key":"3467_CR1","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1016\/S0140-6736(24)00651-2","volume":"403","author":"ND James","year":"2024","unstructured":"James ND, Tannock I, N\u2019Dow J, Feng F, Gillessen S, Ali SA, et al. 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All protocols were approved by the Ethics Committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University (SYSKY-2023-659-01), and informed consent was obtained from all patients or their relatives prior to participation. All in vivo protocols were approved by the Animal Ethical and Welfare Committee of Sun Yat-sen Memorial Hospital (BAP20230673).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The content of this manuscript has not been previously published and is not under consideration for publication elsewhere.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"218"}}