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Article

Defining a Correlative Transcriptional Signature Associated with Bulk Histone H3 Acetylation Levels in Adult Glioblastomas

by
Irati Hervás-Corpión
1,2,
Jorge Navarro-Calvo
3,
Paula Martín-Climent
3,
Marianela Iriarte-Gahete
4,
Noelia Geribaldi-Doldán
5,
Carmen Castro
5 and
Luis M. Valor
3,*
1
Unidad de Investigación, Hospital Universitario Puerta del Mar, INiBICA, 11009 Cádiz, Spain
2
Programa de Tumores Sólidos, Centro de Investigación Médica Aplicada (CIMA), Clínica Universidad de Navarra, 31008 Pamplona, Spain
3
Unidad de Investigación, Hospital General Universitario Dr. Balmis, ISABIAL, 03010 Alicante, Spain
4
Servicio de Inmunología, Hospital Universitario Puerta del Mar, 11009 Cádiz, Spain
5
Facultad de Medicina, Universidad de Cádiz, INiBICA, 11003 Cádiz, Spain
*
Author to whom correspondence should be addressed.
Cells 2023, 12(3), 374; https://doi.org/10.3390/cells12030374
Submission received: 26 December 2022 / Revised: 11 January 2023 / Accepted: 16 January 2023 / Published: 19 January 2023
(This article belongs to the Special Issue Cell Methods: Molecular Events in the Progression of Human Tumor Cell Lines)
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Abstract

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.
Keywords: glioma; epigenetics; histone; acetylation; RNA-seq; HDACi; TSA glioma; epigenetics; histone; acetylation; RNA-seq; HDACi; TSA

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MDPI and ACS Style

Hervás-Corpión, I.; Navarro-Calvo, J.; Martín-Climent, P.; Iriarte-Gahete, M.; Geribaldi-Doldán, N.; Castro, C.; Valor, L.M. Defining a Correlative Transcriptional Signature Associated with Bulk Histone H3 Acetylation Levels in Adult Glioblastomas. Cells 2023, 12, 374. https://doi.org/10.3390/cells12030374

AMA Style

Hervás-Corpión I, Navarro-Calvo J, Martín-Climent P, Iriarte-Gahete M, Geribaldi-Doldán N, Castro C, Valor LM. Defining a Correlative Transcriptional Signature Associated with Bulk Histone H3 Acetylation Levels in Adult Glioblastomas. Cells. 2023; 12(3):374. https://doi.org/10.3390/cells12030374

Chicago/Turabian Style

Hervás-Corpión, Irati, Jorge Navarro-Calvo, Paula Martín-Climent, Marianela Iriarte-Gahete, Noelia Geribaldi-Doldán, Carmen Castro, and Luis M. Valor. 2023. "Defining a Correlative Transcriptional Signature Associated with Bulk Histone H3 Acetylation Levels in Adult Glioblastomas" Cells 12, no. 3: 374. https://doi.org/10.3390/cells12030374

APA Style

Hervás-Corpión, I., Navarro-Calvo, J., Martín-Climent, P., Iriarte-Gahete, M., Geribaldi-Doldán, N., Castro, C., & Valor, L. M. (2023). Defining a Correlative Transcriptional Signature Associated with Bulk Histone H3 Acetylation Levels in Adult Glioblastomas. Cells, 12(3), 374. https://doi.org/10.3390/cells12030374

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