RT journal article
T1 Defining a Correlative Transcriptional Signature Associated with Bulk Histone H3 Acetylation Levels in Adult Glioblastomas
A1 Hervás Corpión, Irati
A1 Navarro Calvo, Jorge
A1 Martín Climent, Paula
A1 Iriarte Gahete, Marianela
A1 Geribaldi Doldán, Noelia
A1 Castro González, Carmen
A1 Valor, Luis M.
A2 Anatomía y Embriología Humana
A2 BiomedicinaBiotecnología y Salud Pública
K1 acetylation
K1 epigenetics
K1 glioma
K1 HDACi
K1 histone
K1 RNA-seq
K1 TSA
AB 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.
PB MDPI
SN 2073-4409
YR 2023
FD 2023-01-19
LK http://hdl.handle.net/10498/31555
UL http://hdl.handle.net/10498/31555
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 08-nov-2026