Chromatin accessibility regulates chemotherapy-induced dormancy and reactivation
| Autor: | Junqi Yi, Lujuan Wang, Jingqun Tang, Anqi Chen, Na Yin, Yaohuan Xie, Qiu Peng, Juanjuan Xiang, Jiaqi Xu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Molecular Therapy: Nucleic Acids, Vol 26, Iss, Pp 269-279 (2021) Molecular Therapy. Nucleic Acids |
| ISSN: | 2162-2531 |
| Popis: | Cisplatin-based chemotherapy remains the standard care for non-small cell lung cancer (NSCLC) patients. Relapse after chemotherapy-induced dormancy affects the overall survival of patients. The evolution of cancer cells under chemotherapy stress is regulated by transcription factors (TFs) with binding sites initially buried deep within inaccessible chromatin. The transcription machinery and dynamic epigenetic alterations during the process of dormancy-reactivation of lung cancer cells after chemotherapy need to be investigated. Here, we investigated the chromatin accessibility of lung cancer cells after cisplatin treatment, using an assay for transposase-accessible chromatin sequencing (ATAC-seq). We observed that global chromatin accessibility was extensively improved. Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST) v.2 was used to elucidate TF-target interaction during the process of dormancy and reactivation. Enhancer regions and motifs specific to key TFs including JUN, MYC, SMAD3, E2F1, SP1, CTCF, SMAD4, STAT3, NFKB1, and KLF4 were enriched in differential loci ATAC-seq peaks of dormant and reactivated cancer cells induced by chemotherapy. The findings suggest that these key TFs regulated gene expressions during the process of dormancy and reactivation of cancer cells through altering promoter accessibility of target genes. Our study helps advance understanding of how cancer cells adapt to the stress induced by chemotherapy through TF binding motif accessibility. Graphical abstract In this study, we profiled chromatin accessibility and transcriptome in cisplatin-responsive dormant and reactivated cells. We observed features of the chromatin landscape of lung cancer cells after chemotherapy. Our integrative analyses revealed that adaptive cellular response is often achieved by transcription factor binding motif accessibility. |
| Databáze: | OpenAIRE |
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