Chromatin accessibility regulates chemotherapy-induced dormancy and reactivation

Lujuan Wang; Qiu Peng; Na Yin; Yaohuan Xie; Jiaqi Xu; Anqi Chen; Junqi Yi; Jingqun Tang; Juanjuan Xiang

Molecular Therapy: Nucleic Acids (Dec 2021)

Chromatin accessibility regulates chemotherapy-induced dormancy and reactivation

Lujuan Wang,
Qiu Peng,
Na Yin,
Yaohuan Xie,
Jiaqi Xu,
Anqi Chen,
Junqi Yi,
Jingqun Tang,
Juanjuan Xiang

Affiliations

Lujuan Wang: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, 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 Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan 410013, China
Qiu Peng: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, 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 Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan 410013, China
Na Yin: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, 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 Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan 410013, China
Yaohuan Xie: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, 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 Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan 410013, China
Jiaqi Xu: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, 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 Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan 410013, China
Anqi Chen: Department of Thoracic Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, Central South University, Changsha, Hunan, China
Junqi Yi: Department of Thoracic Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, Central South University, Changsha, Hunan, China
Jingqun Tang: Department of Thoracic Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, Central South University, Changsha, Hunan, China
Juanjuan Xiang: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, 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 Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan 410013, China; Corresponding author: Juanjuan Xiang, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, China.

Journal volume & issue: Vol. 26
pp. 269 – 279

Abstract

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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.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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