Abstract
Abstract Lung cancer is the leading cause of cancer-related deaths worldwide. A major issue for clinicians and patients alike is inherent resistance to radiation therapy. Recently, certain long non-coding RNAs (lnc-RNAs) have been shown to regulate pathways involved in resistances to lung cancer treatments. Our group recently published that a group of long non-coding RNAs, named the linc-SPRY3 family, play an important role in radiation therapy sensitivity. Originating from the Y-Chromosome, these long non-coding RNAs have been shown in vitro and in vivo to decrease the tumor burden after radiation. Interestingly, certain male Non-Small Cell Lung Cancer (NSCLC) cell lines have been shown to have complete loss of the Y-chromosome (LOY), showing a radiation resistant phenotype. To test this, the DYZ1 region of the Y-chromosome, where the linc-SPRY3 family is expressed, was artificially introduced into radiation resistant male NSCLC cell lines with LOY. Remarkably, by adding the DYZ1 region of the Y-chromosome into these cells, they became more sensitive to radiation and had increased apoptosis. Based on this preliminary data, we hypothesize the linc-SPRY3 family interacts with important pathways in the cell to increase sensitivity to DNA double strand breaks. Through RNA-Sequencing and other preliminary experiments, we found that the linc-SPRY3 family regulates the expression of Cell Division Cycle 6 (CDC6) and Cell Division Cycle 25A (CDC25A) genes. Preliminary data suggests these interactions play a role in influencing NSCLC ability to invade and metastasize. We are currently characterizing this family of linc-RNAs by flow cytometry, in vivo metastasis models, and fluorescent in situ hybridization. We will characterize the mechanism of the linc-SPRY3 family in radiation resistance through genetic modifications and further downstream analysis via the over-expression and knockdown of these linc-RNAs. The characterization of these linc-RNAs will be critical for the development of potential diagnostic or therapeutic therapies. Citation Format: Emily S. Westemeier-Rice. Characterizing the role of the y chromosome-expressed long non-coding RNA linc-SPRY3 family in lung cancer radiation resistance. [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 3751.
Published Version
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