Academic Journal
Defining a Correlative Transcriptional Signature Associated with Bulk Histone H3 Acetylation Levels in Adult Glioblastomas
العنوان: | Defining a Correlative Transcriptional Signature Associated with Bulk Histone H3 Acetylation Levels in Adult Glioblastomas |
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المؤلفون: | Hervás Corpión, Irati, Navarro Calvo, Jorge, Martín Climent, Paula, Iriarte Gahete, Marianela, Geribaldi Doldán, Noelia, Castro González, Carmen, Valor, Luis M. |
المساهمون: | Anatomía y Embriología Humana, Biomedicina, Biotecnología y Salud Pública |
المصدر: | Cells. Vol. 12, nº 3, February 2023, 374 |
بيانات النشر: | MDPI |
سنة النشر: | 2024 |
المجموعة: | RODIN - Repositorio de Objetos de Docencia e Investigación de la Universidad de Cádiz |
مصطلحات موضوعية: | acetylation, epigenetics, glioma, HDACi, histone, RNA-seq, TSA |
الوصف: | Glioblastoma (GB) is the most prevalent primary brain cancer and the most aggressive form of glioma because of its poor prognosis and high recurrence. To confirm the importance of epigenetics in glioma, we explored The Cancer Gene Atlas (TCGA) database and we found that several histone/DNA modifications and chromatin remodeling factors were affected at transcriptional and genetic levels in GB compared to lower-grade gliomas. We associated these alterations in our own cohort of study with a significant reduction in the bulk levels of acetylated lysines 9 and 14 of histone H3 in high-grade compared to low-grade tumors. Within GB, we performed an RNA-seq analysis between samples exhibiting the lowest and highest levels of acetylated H3 in the cohort; these results are in general concordance with the transcriptional changes obtained after histone deacetylase (HDAC) inhibition of GB-derived cultures that affected relevant genes in glioma biology and treatment (e.g., A2ML1, CD83, SLC17A7, TNFSF18). Overall, we identified a transcriptional signature linked to histone acetylation that was potentially associated with good prognosis, i.e., high overall survival and low rate of somatic mutations in epigenetically related genes in GB. Our study identifies lysine acetylation as a key defective histone modification in adult high-grade glioma, and offers novel insights regarding the use of HDAC inhibitors in therapy. ; 15 páginas |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 2073-4409 |
Relation: | info:eu-repo/grantAgreement/MINECO//CP15%2F00180/ES/CP15%2F00180/; info:eu-repo/grantAgreement/MINECO//PI16%2F00722/ES/Biomarcadores y dianas del núcleo celular en enfermedades neurodegenerativas de trinucleótidos/; info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F00125/ES/BIOMARCADORES ESPECIFICOS DE TIPO CELULAR EN FLUIDOS PERIFERICOS DE ENFERMEDADES DE TRINUCLEOTIDOS/; http://hdl.handle.net/10498/31555 |
DOI: | 10.3390/cells12030374 |
الاتاحة: | http://hdl.handle.net/10498/31555 https://doi.org/10.3390/cells12030374 |
Rights: | Atribución 4.0 Internacional ; http://creativecommons.org/licenses/by/4.0/ ; open access |
رقم الانضمام: | edsbas.176C54A |
قاعدة البيانات: | BASE |
تدمد: | 20734409 |
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DOI: | 10.3390/cells12030374 |