Chromatin accessibility is associated with therapeutic response in prostate cancer

Lee,Sanghoon; Lee,Da Young; So,Insuk; Chun,Jung Nyeo; Jeon,Ju-Hong

doi:10.3892/ol.2024.14738

Chromatin accessibility is associated with therapeutic response in prostate cancer

Authors:
- Sanghoon Lee
- Da Young Lee
- Insuk So
- Jung Nyeo Chun
- Ju-Hong Jeon
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Affiliations: Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
Published online on: October 14, 2024 https://doi.org/10.3892/ol.2024.14738
Article Number: 605
Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Treatment of advanced prostate cancer is challenging due to a lack of effective therapies. Therefore, it is important to understand the molecular mechanisms underlying therapeutic resistance in prostate cancer and to identify promising drug targets offering significant clinical advantages. Given the pivotal role of dysregulated transcriptional programs in the therapeutic response, it is essential to prioritize translational efforts targeting cancer‑associated transcription factors (TFs). The present study investigated whether chromatin accessibility was associated with therapeutic resistance in prostate cancer using Assay for Transposase‑Accessible Chromatin with sequencing (ATAC‑seq) data. The bioinformatics analysis identified differences in chromatin accessibility between the drug response (Remission) and drug resistance (Disease) groups. Additionally, a significant association was observed between chromatin accessibility, transcriptional output and TF activity. Among TFs, forkhead box protein M1 (FOXM1) was identified as a TF with high activity and expression in the Disease group. Notably, the results of the computational analysis were validated by FOXM1 knockdown experiments, which resulted in suppressed cell proliferation and enhanced therapeutic sensitivity in prostate cancer cells. The present findings demonstrated that chromatin accessibility and TF activity may be associated with therapeutic resistance in prostate cancer. Additionally, these results provide the basis for future investigations aimed at understanding the molecular mechanisms of drug resistance and developing novel therapeutic approaches for prostate cancer.

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