Abstract 4115: Gene expression and bioinformatics profiles of four different cancer cells following treatment with HDAC inhibitor SAHA
Authors: Umamaheswari Natarajan, Appu Rathinavelu
Journal: Cancer Research (2025)

Abstract Background: Epigenetic modifications of chromatin play a crucial role in regulating gene expression and are often dysregulated in cancer. This study aimed to investigate changes in gene expressions following HDAC (Histone Deacetylase) inhibition in breast, ovarian, and lung cancer cells. Aim: Our goal was to determine and compare the epigenetic alteration related gene expressions that may serve as diagnostic and/or predictive biomarkers for human cancers. To achieve this, we evaluated the effect of SAHA treatment on histone and DNA modification related gene expressions in human breast (MCF7), ovarian (A2780), and lung (HCC827 &amp; H460) cancer cell lines. Method: Using RT2 Profiler PCR Array, we identified the differential expression of genes (DEGs) in four different human cancer cells following SAHA treatment in comparison to untreated controls. Independent quantitative real-time PCR (qRT-PCR) verified some of the most significant DEGs. We constructed a protein-protein interaction (PPI) network using STRING and Cytoscape to analyze the interactions of these DEGs. Results: Our results showed that SAHA exposure significantly impacted histone and DNA modification related methyltransferases in the above listed human cancer cells. We identified three differentially expressed genes, including two commonly down-regulated (DNMT3A, NSD1) and one significantly up-regulated (HDAC3) genes in these cancer cells that were treated with SAHA. qRT-PCR and Western blot analyses confirmed the array results of DNMT3A, NSD1 and along with USP21, PAK1, and NEK6. All levels of all these five proteins were significantly down regulated following treatment with SAHA. Conclusion: Our study demonstrates some commonality in the DEGs and the impact of HDAC inhibition with SAHA in four different human cancer cells compared with normal cells. Our findings provide new insights into the network and the interactions of significantly altered gene expressions that may eventually impact the growth abilities of cancer cells. Our findings also highlight some of the potential molecular targets and related signaling pathways. Altogether, these results may also contribute to our better understanding of the HDAC inhibition related mechanisms that may underly the growth regulation of breast, ovarian, and lung cancer cells. Acknowledgements: This project was supported by the NSU’s President's Faculty Research and Development Grant (PFRDG), This research was partially funded by a Bankhead Coley Infrastructure Development Grant from the Florida Department of Health of the State of Florida that was awarded to A.R. through the Department of Pharmacology of the University of Miami, Coral Gables, Florida, USA, was used for this project, and also the authors would like to thank Royal Dames of Cancer Research, Inc. (Ft. Lauderdale, FL, USA) for their financial support in conducting this research. Citation Format: Umamaheswari Natarajan, Appu Rathinavelu. Gene expression and bioinformatics profiles of four different cancer cells following treatment with HDAC inhibitor SAHA [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 4115.