Abstract 1503: Elucidating the role of transcription coregulator MED15 in cancer cell oxidative stress response and proliferation

Abstract Hyperproliferation is a hallmark of cancer that leads to increased ROS levels, leading to oxidative stress, which causes DNA damage and reinforces cell proliferation. To grow in these conditions, cancer cells activate cellular pathways to rewire the transcriptome to promote oxidative stress resistance. Mapping these response pathways can lead to potential new drugs. Mediator complex subunit MED15 is upregulated in many cancer types and confers oxidative stress resistance in lower animals. To test if MED15 promotes oxidative stress resistance in cancer, we generated three MED15 knockout A549 lung adenocarcinoma cells. Transcriptome, real-time quantitative PCR, and Western Blot analysis showed that MED15 loss downregulates oxidative stress response genes, both at baselines and after stress-inducing compounds. Furthermore, the MED15 knockouts were observed to proliferate slower, so I performed cell cycle analysis using flow cytometry which showed that MED15 knockouts arrest cell cycle more after serum starvation compared to their wild-type counterparts. In sum, our data indicate that MED15 is required for normal cancer cell stress resistance and growth. This has clinical potential, as MED15 can be targeted by small molecules, making it a promising drug target. Citation Format: Chiaki Shuzenji, Xuanjin Cheng, Stefan Taubert. Elucidating the role of transcription coregulator MED15 in cancer cell oxidative stress response and proliferation [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 1503.