GINS2 regulates temozolomide chemosensitivity via the EGR1/ECT2 axis in gliomas

• DOI: 10.1038/s41419-024-06586-w
• Publication Date: 2024-03-11T16:02:54Z
• Authors: Hua He; Lu Liang; Shiyao Jiang; Yueying Liu; Jingjing Huang; Xiaoyan Sun; Yi Li; Yiqun Jiang; Li Cong
• Keywords: Temozolomide

Abstract Temozolomide (TMZ), a DNA alkylating agent, has become the primary treatment for glioma, most common malignancy of central nervous system. Although TMZ-containing regimens produce significant clinical response rates, some patients inevitably suffer from inferior outcomes or disease relapse, likely because poor chemosensitivity glioma cells due to robust damage (DDR). GINS2, subunit helicase, contributes maintaining genomic stability and is highly expressed in various cancers, promoting their development. Here, we report that GINS2 was upregulated TMZ-treated co-localized with γH2AX, indicating its participation TMZ-induced DDR. Furthermore, regulated malignant phenotype TMZ sensitivity cells, mostly by repair affecting mRNA early growth factor 1 (EGR1), which turn regulates transcription epithelial cell-transforming sequence 2 (ECT2). We constructed GINS2–EGR1–ECT2 prognostic model, accurately predicted patient survival. Further, screened Palbociclib/BIX-02189 dampens expression synergistically inhibits cell proliferation TMZ. These findings delineate novel mechanism propose promising combination therapy treat glioma.