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- Title
GINS2 regulates temozolomide chemosensitivity via the EGR1/ECT2 axis in gliomas.
- Authors
He, Hua; Liang, Lu; Jiang, Shiyao; Liu, Yueying; Huang, Jingjing; Sun, Xiaoyan; Li, Yi; Jiang, Yiqun; Cong, Li
- 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.
- Publication
Cell Death & Disease, 2024, Vol 15, Issue 3, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-024-06586-w