Abstract LB198: The PAX5 oncogene encodes circular RNA products involved in B cell cancer processes
Bibliographic record
Abstract
Abstract Introduction: B-cell cancers represent some of the most prevalent hematological lesions in adult and children. B-cell cancers are also notable for their malignancy and resistance to drug therapies. Our group studies B-cell oncogenes and recently discovered that the prominent PAX5 oncogene, which usually encodes transcription factors, also generates non-coding circular RNA transcripts. Circular RNAs (circRNAs) represent a new class of gene products involved in many biological processes and cancer disease. Due to their innate ability to bind and modulate co-interacting proteins and microRNAs (miRs), circRNAs represent new signaling avenues in cancer biology. Hypothesis: Given that products from the PAX5 oncogene are important regulators of B-cell cancers, we hypothesized that PAX5 circRNAs (circPAX5) are also involved in B-cell oncogenesis. Objective: We therefore set out to study circPAX5 products, and their co-interacting miRs, in B-cell cancers. Results: Using a series of B-cell cancer models and clinical samples, we first profiled the expression of circPAX5 products and found that B-cell leukemias overexpress circPAX5 where its predominant circRNA isoform consisted of exons 2 to 5 sequences of the PAX5 locus. To establish a functional role of circPAX5 on cancer processes, we evaluated B-cell proliferation and chemosensitivity in cancer models expressing conditioned levels of circPAX5. Interestingly, we found that the suppression of circPAX5 levels resulted in the alteration of cancer growth rates, which were dependent upon B-cell differentiation state and population subtype. Mechanistically, we also found that circPAX5 interacts with specific miRs, which were profiled by circRNA precipitation and deep sequencing. Selected sponged miRs were then studied by bio-informatic analyses and mapped to downstream mRNA targets and B-cell cancer pathways. Conclusions: Altogether, our findings uncover PAX5 circular products, which are involved in B-cell cancer processes and could potentially represent a new cancer pathway targeted for therapeutic and/or diagnostic strategies in B-cell cancer lesions. Citation Format: Danick Martin, Brandon Hannay, Farrah McGraw, Alexis Martin, Vanessa Veilleux, Nicholas Finn, Gilles A. Robichaud. The PAX5 oncogene encodes circular RNA products involved in B cell cancer processes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB198.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".