Abstract
Abstract Circular RNAs (circRNAs) represent a new class of gene products involved in many biological processes. Due to their ability to bind and modulate co-interacting proteins and microRNAs (miRs), circRNAs represent new signaling mediators in cell biology and cancer processes. Recently, we identified circRNAs from the PAX5 oncogene (circPAX5) in B-cells. Given that PAX5 gene products are well established as potent oncogenic regulators of B-cell cancer lesions, we hypothesized that circPAX5 may also be potentially involved in pathogenic processes of B-cell malignancies. In this study, we wanted to understand the role of circPAX5 in B-cell cancer processes and elucidate new potential targets for diagnostic and therapeutic avenues. Using a series of B-cell cancer models and clinical samples, we sequenced, mapped, and profiled circPAX5 expression profiles and found that circPAX5 products are indeed overexpressed in various cancer cell types where the predominant expressed isoform consisted of exons 2 to 5 (circPAX5_2-5) of the PAX5 locus. In addition, we isolated circPAX5 complexes from cancer cells and identified co-interacting small non-coding RNAs, notably microARNs (miRs) by deep sequencing. To further elucidate the functional role of circPAX5 and miR co-interactions, selected miRs from the list were then conditionally overexpressed in B-cells followed by cellular phenotypic assays. Altogether, our results characterize new signaling products and pathways in B-cells. Our data also suggests that circPAX5 products are involved in B-cell cancer processes and could potentially represent new cancer pathways targeted for strategic therapeutic and/or diagnostic strategies in B-cell cancer lesions Citation Format: Danick M. Martin, Brandon Hannay, Alexis Martin, Vanessa Veilleux, Nicholas Finn, Gilles A. Robichaud. Circular RNAs from the PAX5 oncogene are overexpressed in B-cell malignancies and modulate cancer processes. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3812.
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