Super enhancer loci of EGFR regulate EGFR variant 8 through enhancer RNA and strongly associate with survival in HNSCCs.

التفاصيل البيبلوغرافية
العنوان:	Super enhancer loci of EGFR regulate EGFR variant 8 through enhancer RNA and strongly associate with survival in HNSCCs.
المؤلفون:	Chakkarappan SR; Department of Health Research, Multi Disciplinary Research Unit (DHR-MRU), Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India., Umadharshini KV; Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India., Dhamodharan S; Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India., Rose MM; Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India., Gopu G; Department of Surgical Oncology, Rajiv Gandhi Government General Hospital, Madras Medical College, Chennai, 600003, India., Murugan AK; Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, 11211, Riyadh, Saudi Arabia., Inoue I; Human Genetics Laboratory, National Institute of Genetics, Mishima, 411-8540, Japan., Munirajan AK; Department of Health Research, Multi Disciplinary Research Unit (DHR-MRU), Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India. akmunirajan@gmail.com.; Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India. akmunirajan@gmail.com.
المصدر:	Molecular genetics and genomics : MGG [Mol Genet Genomics] 2024 Jan 18; Vol. 299 (1), pp. 3. Date of Electronic Publication: 2024 Jan 18.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 101093320 Publication Model: Electronic Cited Medium: Internet ISSN: 1617-4623 (Electronic) Linking ISSN: 16174623 NLM ISO Abbreviation: Mol Genet Genomics Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Berlin : Springer-Verlag, c2001-
مواضيع طبية MeSH:	Enhancer RNAs* , Head and Neck Neoplasms*/genetics, Humans ; Squamous Cell Carcinoma of Head and Neck ; Super Enhancers ; ErbB Receptors/genetics ; Chromatin/genetics
مستخلص:	Epidermal growth factor receptor (EGFR) has been shown to be overexpressed in human cancers due to mutation, amplification, and epigenetic hyperactivity, which leads to deregulated transcriptional mechanism. Among the eight different EGFR isoforms, the mechanism of regulation of full-length variant 1 is well-known, no studies have examined the function & factors regulating the expression of variant 8. This study aimed to understand the function of EGFR super-enhancer loci and its associated transcription factors regulating the expression of EGFR variant 8. Our study shows that overexpression of variant 8 and its transcription was more prevalent than variant 1 in many cancers and positively correlated with the EGFR-AS1 expression in oral cancer and HNSCC. Notably, individuals overexpressing variant 8 showed shorter overall survival and had a greater connection with other clinical traits than patients with overexpression of variant 1. In this study, TCGA enhancer RNA profiling on the constituent enhancer (CE1 and CE2) region revealed that the multiple enhancer RNAs formed from CE2 by employing CE1 as a promoter. Our bioinformatic analysis further supports the enrichment of enhancer RNA specific chromatin marks H3K27ac, H3K4me1, POL2 and H2AZ on CE2. GeneHancer and 3D chromatin capture analysis showed clustered interactions between CE1, CE2 loci and this interaction may regulates expression of both EGFR-eRNA and variant 8. Moreover, increased expression of SNAI2 and its close relationship to EGFR-AS1 and variant 8 suggest that SNAI2 could regulates variant 8 overexpression by building a MegaTrans complex with both EGFR-eRNA and EGFR-AS1. Our findings show that EGFR variant 8 and its transcriptional regulation & chromatin modification by eRNAs may provide a rationale for targeting RNA splicing in combination with targeted EGFR therapies in cancer. (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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معلومات مُعتمدة:	No. V.25011/536-HRD/2016-HR Department of Health Research, New Delhi, India; 1A2022 National Institute of Genetics Japan
فهرسة مساهمة:	Keywords: Chromatin; CpG; EGFR; EGFR-AS1; H3K27ac; eRNA
المشرفين على المادة:	0 (Enhancer RNAs) EC 2.7.10.1 (ErbB Receptors) 0 (Chromatin) EC 2.7.10.1 (EGFR protein, human)
تواريخ الأحداث:	Date Created: 20240118 Date Completed: 20240119 Latest Revision: 20240119
رمز التحديث:	20240119
DOI:	10.1007/s00438-023-02089-z
PMID:	38236481
قاعدة البيانات:	MEDLINE

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تدمد:	1617-4623
DOI:	10.1007/s00438-023-02089-z