Abstract LB313: Inflammatory cytokines and extracellular matrix remodeling genes are epigenetically regulated in neoplastic HK-2 cells transformed by chronic exposure to arsenic

Abstract Arsenic is an environmental carcinogen. Epidemiological studies suggest that chronic exposure to lower levels of arsenic is associated with kidney cancer in human population. Increased proliferation, cellular remodeling by epithelial-mesenchymal transition and stemness contribute to neoplastic transformation of cells. Additionally, the aberrant expression of Inflammatory cytokines and extracellular matrix (ECM) related genes are known to mediate these changes. However, the underlying mechanism for altered expression of these genes is not fully understood. Overwhelming evidence suggest that epigenetic dysregulation leads to cancer development. Therefore, the objective of this was to investigate if arsenic induces the epigenetic dysregulation of cytokines and ECM related genes during malignant transformation. Using HK-2 kidney epithelial cells malignantly transformed by chronic arsenic exposure, gene expressions were analyzed by qRT-PCR. The result of this study revealed aberrant expression of genes for inflammatory cytokines and ECM in these cells. DNA demethylating agent 5 Aza 2-deoxycytidine and histone deacetylase inhibitor Trichostatin A restored the expression of cytokines and ECM related genes. Changes in the levels of modified histone H3 with gene activating and repressing marks were observed. To further evaluate the role of histone modifications in gene regulation, ChIP-qRT-PCR was performed to determine the binding of Histone H3 with gene activating and repressive marks to the promoter regions of inflammatory cytokines and ECM related genes. The result revealed several fold changes in H3K9ac and H3K9me2-bound promoter DNA in arsenic exposed cells as compared to control cells. This suggests aberrant expression of genes is regulated by these histone marks. In summary, the findings of this study suggest epigenetic regulation of inflammatory cytokines and ECM related genes expression by changes in histone marks during arsenic induced neoplastic transformation of HK-2 cells. Citation Format: Priti Roy, Kamaleshwar Prasad Singh. Inflammatory cytokines and extracellular matrix remodeling genes are epigenetically regulated in neoplastic HK-2 cells transformed by chronic exposure to arsenic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB313.