GINS2 regulates temozolomide chemosensitivity via the EGR1/ECT2 axis in gliomas.
Cell Death Dis
; 15(3): 205, 2024 Mar 11.
Article
in En
| MEDLINE
| ID: mdl-38467631
ABSTRACT
Temozolomide (TMZ), a DNA alkylating agent, has become the primary treatment for glioma, the most common malignancy of the central nervous system. Although TMZ-containing regimens produce significant clinical response rates, some patients inevitably suffer from inferior treatment outcomes or disease relapse, likely because of poor chemosensitivity of glioma cells due to a robust DNA damage response (DDR). GINS2, a subunit of DNA helicase, contributes to maintaining genomic stability and is highly expressed in various cancers, promoting their development. Here, we report that GINS2 was upregulated in TMZ-treated glioma cells and co-localized with γH2AX, indicating its participation in TMZ-induced DDR. Furthermore, GINS2 regulated the malignant phenotype and TMZ sensitivity of glioma cells, mostly by promoting DNA damage repair by affecting the mRNA stability of early growth response factor 1 (EGR1), which in turn regulates the transcription of epithelial cell-transforming sequence 2 (ECT2). We constructed a GINS2-EGR1-ECT2 prognostic model, which accurately predicted patient survival. Further, we screened Palbociclib/BIX-02189 which dampens GINS2 expression and synergistically inhibits glioma cell proliferation with TMZ. These findings delineate a novel mechanism by which GINS2 regulates the TMZ sensitivity of glioma cells and propose a promising combination therapy to treat glioma.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Neoplasms
/
Glioma
Limits:
Humans
Language:
En
Journal:
Cell Death Dis
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: