Data · dataset · 2023
SETD2 Palmitoylation Mediated by ZDHHC16 in Epidermal Growth Factor Receptor-Mutated Glioblastoma Promotes Ionizing Radiation-Induced DNA Damage
Listed in ScienceDB
Purpose: The prevalence of epidermal growth factor receptor (EGFR) mutations in glioblastoma multiforme (GBM) has elicited a significant focus on EGFR as a potential drug target.
Description
However, no significant clinical advancement in GBM treatment has occurred.Methods and materials: Bioinformatics analysis, western blotting, immunofluorescence, and immunohistochemistry were performed to detect the expression of ZDHHC16 and genetic EGFR alterations in GBM.
The biological function of ZDHHC16/SETD2/H3K36me3 signaling axis after EGFR alterations was demonstrated by various in vitro (pharmacologic treatment, flow cytometry, transwell migration assay, and coimmunoprecipitation) and in vivo (xenograft model) experiments.Results: We demonstrate that the ZDHHC16/SETD2/H3K36me3 signaling axis was inactivated in EGFR-altered GBM. ZDHHC16 was downregulated in GBM versus normal brain tissue; this was significantly related to EGFR alterations.
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These events contributed to p53 activation, halting cells at the G1/S checkpoint. Furthermore, DNA damage repair signaling in EGFR-amplified GBMs was affected after ionizing radiation-induced DNA damage via reduced SETD2 palmitoylation and methylation of its target, H3K36. Our findings suggest that a depalmitoylation inhibitor, PalmB, is useful as a potentially novel adjuvant treatment for patients with GBM undergoing radiation therapy.Conclusions: Our data present novel mechanistic evidence relating to signaling pathways with DNA damage responses in EGFR-mutated GBM.
Links
Where it is published
- DOI doi.org/10.57760/sciencedb.11065 ↗
DOI / persistent id · from scidb cn
Catalogue records · 1
- OAI-PMH record scidb.cn/oai?verb=GetRecord&metadataPrefix=oai_dc&identifier=10.57760%2… ↗
metadata API · from scidb cn
Topics
- From keywords
- Earth & Environmental Science · Engineering · Humanities · Life Sciences · Social Science
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| ScienceDB | 10.57760/sciencedb.11065 | 10 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · scidb cn | connector:scidb_cn@1.0.0 | |
| concepts[field].local:field:earth-environmental | mapping · scidb cn | connector:scidb_cn@1.0.0 | |
| concepts[field].local:field:engineering | mapping · scidb cn | connector:scidb_cn@1.0.0 | |
| concepts[field].local:field:humanities | mapping · scidb cn | connector:scidb_cn@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · scidb cn | connector:scidb_cn@1.0.0 | |
| concepts[field].local:field:social-science | mapping · scidb cn | connector:scidb_cn@1.0.0 | |
| description | source · scidb cn | connector:scidb_cn@1.0.0 | /metadata/dc/description |
| license | source · scidb cn | connector:scidb_cn@1.0.0 | /metadata/dc/rights |
| publication_date | source · scidb cn | connector:scidb_cn@1.0.0 | |
| title | source · scidb cn | connector:scidb_cn@1.0.0 | /metadata/dc/title |