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

Hua He1,2, Lu Liang1,2, Shiyao Jiang1,2

  • 1The Key Laboratory of Model Animal and Stem Cell Biology in Hunan Province, Hunan Normal University, Changsha, 410013, Hunan, China.

Cell Death & Disease
|March 12, 2024
PubMed

Insights

GINS2 enhances glioma cell resistance to temozolomide (TMZ) by promoting DNA repair. Targeting GINS2 with Palbociclib/BIX-02189 offers a promising combination therapy for glioma treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Temozolomide (TMZ) is a primary treatment for glioma, a common brain tumor.
  • Glioma patients often experience treatment failure due to robust DNA damage response (DDR), leading to poor chemosensitivity.
  • GINS2, a DNA helicase subunit, is upregulated in cancers and linked to genomic instability.

Purpose of the Study:

  • To investigate the role of GINS2 in temozolomide resistance in glioma.
  • To identify novel therapeutic targets and strategies for improving glioma treatment outcomes.

Main Methods:

  • Analysis of GINS2 expression in TMZ-treated glioma cells.
  • Investigation of GINS2's role in DNA damage repair and cell phenotype.
  • Construction of a GINS2-EGR1-ECT2 prognostic model.
  • Screening for drugs that inhibit GINS2 expression and enhance TMZ efficacy.

Main Results:

  • GINS2 expression is upregulated in glioma cells upon TMZ treatment and participates in TMZ-induced DDR.
  • GINS2 promotes DNA damage repair by regulating EGR1 mRNA stability, impacting ECT2 transcription.
  • The GINS2-EGR1-ECT2 model accurately predicts patient survival.
  • Palbociclib/BIX-02189 was identified to dampen GINS2 expression and synergize with TMZ to inhibit glioma cell proliferation.

Conclusions:

  • GINS2 plays a critical role in regulating glioma cell chemosensitivity to TMZ by modulating DNA repair pathways.
  • The GINS2-EGR1-ECT2 axis represents a novel mechanism influencing glioma progression and prognosis.
  • Targeting GINS2 with agents like Palbociclib/BIX-02189 in combination with TMZ presents a promising therapeutic strategy for glioma.

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