Abstract 5179: Investigating the tumor suppressive role of RanBP9 in mice deficient in p53
Bibliographic record
Abstract
Abstract RAN binding protein 9 (RanBP9) is a scaffolding protein that is essential for the formation a multi-subunit E3 ubiquitin ligase termed the C-terminal to Lis-1 homology (CTLH) complex. Multiple groups have identified the CTLH complex in regulating a broad range of biological processes including cell cycle, cell proliferation, and metabolism. Various studies have demonstrated that RanBP9 functions as a tumor suppressor, but none have shown whether the loss of RanBP9 can initiate spontaneous tumor formation. Here, we investigated the tumor suppressive role of RanBP9 in C57BL/6 mice. Bulk RNA sequencing (RNA-seq) analysis of 1-month-old RanBP9-/- mice liver identified an upregulation of several oncogenic signaling genes. Although RanBP9-/- mice displayed a shortened lifespan, these mice did not develop spontaneous tumors suggesting that additional genetic perturbations are required for tumor development. Next, we conducted an observational study in mice with RanBP9+/-: Trp53+/- (R9; p53+/-) and RanBP9-/-: Trp53-/- (R9; p53-/-) genotypes. These mice were monitored over 17 months for the development of spontaneous tumors. The primary endpoint was defined as the development of a visible mass (>1.5 cm) or symptoms of cancer. R9; p53+/- mice (n=23) developed sarcomas at an earlier time compared to control p53+/- mice (n=18; p<0.05). R9; p53+/- mice displayed altered tumor spectrum with increased frequency in soft tissue sarcoma (STS) development. H&E analysis of tumor biopsies revealed increased mitotic activity of sarcomas derived from R9; p53+/- mice compared to control p53+/- mice. We observed no significant difference in tumor incidence and altered tumor spectrum in R9; p53-/- mice compared to control p53-/- mice. Analysis of TCGA sarcoma database revealed a correlation between low gene expression of CTLH complex genes and reduced survival in sarcoma patients. Our data indicates that loss of RanBP9 alone is insufficient to initiate tumor development. However, the heterozygous loss of RanBP9 and p53 promotes increased STS development. Ongoing efforts are to further characterize R9; p53+/- tumors and identify the mechanism to understand how the loss of CTLH activity contributes to sarcoma development in the absence of p53. Our findings may support the development of anti-cancer therapeutics that activates RanBP9-CTLH complex activity. Citation Format: Brianna Gonga-Cave, Gabriel Onea, Xu Wang, Sean Cregan, Patti Kaiser, Caroline Schild-Poulter. Investigating the tumor suppressive role of RanBP9 in mice deficient in p53 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5179.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".