ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
A novel protein encoded by circIMP3 promotes prostate cancer progression by regulating alternative splicing and tumor microenvironment
Provisionally accepted
- 1Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- 2Nanjing University of Chinese Medicine, Nanjing, China
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Prostate cancer (PC) is one of the most common malignancies in men, with increasing incidence and mortality worldwide. Despite the development of multiple therapeutic strategies, including androgen deprivation therapy and chemotherapy, effective cures remain limited, particularly in advanced stages. Recent evidence highlights the critical roles of alternative splicing (AS) and non-coding RNAs—especially circular RNAs (circRNAs)—in tumor progression and resistance. In this study, we identify a novel circRNA derived from the IMP3 gene, termed circIMP3, which is significantly upregulated in PC tissues and patient blood samples. Notably, circIMP3 harbors an internal ribosome entry site (IRES) and encodes a previously uncharacterized 288-amino-acid protein, circIMP3_288aa. Functional assays revealed that circIMP3_288aa promotes proliferation of PC cells in vitro and accelerates tumor growth in vivo. Mechanistically, circIMP3_288aa regulates FBXW7 exon skipping, leading to impaired c-Myc ubiquitination and enhanced c-Myc stabilization, thus promoting oncogenic signaling. RNA immunoprecipitation sequencing (RIP-seq) identified over 2,000 IMP3-regulated AS events, with significant enrichment in ubiquitin-mediated proteolysis pathways. Importantly, circIMP3 is actively secreted via exosomes into the tumor microenvironment (TME), where it is taken up by recipient cells and translated into circIMP3_288aa, thereby enhancing their proliferation. Our findings demonstrate a dual role for circIMP3: as an intracellular regulator of alternative splicing and as a paracrine signal in the TME. Clinically, high circIMP3 expression correlates with poorer event-free survival in PC patients and is detectable in peripheral blood, highlighting its potential as a prognostic biomarker and liquid biopsy target.
Keywords: prostate cancer, circular RNA, Alternative Splicing, IMP3, Fbxw7, c-Myc
Received: 11 Oct 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Zuo, Huang, Chen, Xu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yang Zhang
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