دورية أكاديمية
The role of JMJD2A in immune evasion and malignant behavior of esophageal squamous cell carcinoma.
| العنوان: | The role of JMJD2A in immune evasion and malignant behavior of esophageal squamous cell carcinoma. |
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| المؤلفون: | Su X; Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China; School of Medicine, Southeast University, Nanjing 210009, China., Ding X; Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China; School of Medicine, Southeast University, Nanjing 210009, China., Ding C; Department of Internal Medicine of Traditional Chinese Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China., Wang G; Department of Pathology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China., Fu C; Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China., Liu F; Department of Medical Oncology, Luhe People's Hospital of Nanjing, Nanjing 210000, China., Shi J; Department of Ultrasound, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China. Electronic address: shijinjun_0@sohu.com., He W; Department of Thoracic surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China. Electronic address: heweicts@126.com. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2024 Aug 20; Vol. 137, pp. 112401. Date of Electronic Publication: 2024 Jun 14. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Esophageal Squamous Cell Carcinoma*/genetics , Esophageal Squamous Cell Carcinoma*/immunology , Esophageal Neoplasms*/genetics , Esophageal Neoplasms*/immunology , Jumonji Domain-Containing Histone Demethylases*/metabolism , Jumonji Domain-Containing Histone Demethylases*/genetics , Gene Expression Regulation, Neoplastic*, Humans ; Cell Line, Tumor ; Radiation Tolerance/genetics ; Immune Evasion ; Tumor Escape ; Ferroptosis/genetics ; Transcription Factors/metabolism ; Transcription Factors/genetics ; Histones/metabolism ; DNA Damage ; DNA Helicases/genetics ; DNA Helicases/metabolism |
| مستخلص: | Objective: This study aimed to investigate the role of JMJD2A in radiotherapy tolerance of esophageal squamous cell carcinoma (ESCC). Methods: The levels of H3K9me3 modification were analyzed in anti-PD-1 therapy non-responder or responder patients, and the expression differences of H3K9me3-related modifying enzymes were assessed in TCGA-ESCC and ICGC cohorts. Subsequently, JMJD2A was knocked down in ESCC cells using CRISPR-Cas9 or lentivirus-mediated shRNA, and changes in malignant behavior of ESCC cells were observed. RNA-seq, ATAC-seq, and ChIP-seq analyses were then conducted to investigate the genes and downstream signaling pathways regulated by JMJD2A, and functional validation experiments were performed to analyze the role of downstream regulated genes and pathways in ESCC malignant behavior and immune evasion. Results: JMJD2A was significantly overexpressed in ESCC and anti-PD-1 therapy non-responders. Knockdown or deletion of JMJD2A significantly promoted the malignant behavior and immune evasion of ESCC. JMJD2A facilitated the structural changes in chromatin and promoted the binding of SMARCA4 to super-enhancers, thereby inducing the expression of GPX4. This resulted in the inhibition of radiation-induced DNA damage and cell ferroptosis, ultimately promoting the malignant behavior and immune evasion of ESCC cells. Conclusion: JMJD2A plays an indispensable role in the malignant behavior and immune evasion of ESCC. It regulates the binding of SMARCA4 to super-enhancers and affects the chromatin's epigenetic landscape, thereby promoting the expression of GPX4 and attenuating iron-mediated cell death caused by radiotherapy. Consequently, it triggers the malignant behavior and immune evasion of ESCC cells. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Esophageal squamous cell carcinoma; Ferroptosis; Immune evasion; JMJD2A; Malignant behavior; SMARCA4 |
| المشرفين على المادة: | EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases) EC 1.5.- (KDM4A protein, human) 0 (Transcription Factors) 0 (Histones) EC 3.6.4.- (DNA Helicases) |
| تواريخ الأحداث: | Date Created: 20240615 Date Completed: 20240710 Latest Revision: 20240805 |
| رمز التحديث: | 20240805 |
| DOI: | 10.1016/j.intimp.2024.112401 |
| PMID: | 38878485 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
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| DOI: | 10.1016/j.intimp.2024.112401 |