Chromatin accessibility regulates chemotherapy-induced dormancy and reactivation

Molecular Therapy: Nucleic Acids

Anqi Chen¹  Qiu Peng¹  Jingqun Tang²  Yaohuan Xie²  Na Yin³  Junqi Yi³  Jiaqi Xu⁴  Lujuan Wang⁴  Juanjuan Xiang⁴ 

[1] Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, China;Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan 410013, China;NHC Key Laboratory of Carcinogenesis and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China;Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;

关键词: NSCLC;    chemotherapy;    dormancy and reactivation;    chromatin accessibility;    transcription factors;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown