ICBP90, an epigenetic regulator, induces DKK3 promoter methylation, promotes glioma progression, and reduces...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genetics

Background:

• Glioma, a common brain malignancy, exhibits high mortality and treatment resistance.
• Inverted CCAAT box Binding Protein of 90 kDa (ICBP90) is implicated in tumor progression and DNA methylation maintenance.

Purpose of the Study:

• To investigate the role of ICBP90 in glioma progression, invasion, and sensitivity to cisplatin (DDP).
• To elucidate the molecular mechanism by which ICBP90 influences glioma cell behavior and drug response.

Main Methods:

• Construction of ICBP90 over-expression and knockdown glioma cell lines.
• In vivo mouse xenograft models to assess tumor growth.
• Analysis of gene expression, DNA methylation, and protein levels (e.g., DKK3, β-catenin, c-Myc, cyclin D1, gasdermin D, caspase 1).

Main Results:

• ICBP90 knockdown inhibited glioma cell proliferation, migration, invasion, and tumor growth.
• ICBP90 silencing enhanced DDP sensitivity and pyroptosis, while over-expression had opposite effects.
• ICBP90 suppressed DKK3 expression via promoter methylation, inhibiting β-catenin signaling and downstream targets (c-Myc, cyclin D1).

Conclusions:

• ICBP90 promotes glioma carcinogenesis and DDP insensitivity by epigenetically silencing DKK3.
• Targeting ICBP90 may represent a therapeutic strategy for overcoming glioma treatment resistance.