A novel polypeptide encoded by circSPIRE1 promotes prostate cancer proliferation and migration by restraining the ubiquitin-dependent degradation of LRP5
Bibliographic record
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".