Research Progress on TRIM28 and GBM

Glioblastoma (GBM) is the most aggressive and deadly malignant glioma of the adult central nervous system (CNS), making the discovery of related genes essential for its treatment and prognosis. Recent study has shown that Tripartite motif (TRIM) is involved in several biological processes, both suppressing tumor formation and facilitating tumor growth and invasion. It may modulate the onset and progression of cancers via many methods. tripartite motif-containing protein 28 (TRIM28) is a member of the TRIM protein family, serving as a multifunctional transcriptional regulator that participates in chromatin remodeling, DNA damage repair, and the maintenance of stem cell pluripotency. Recent research indicates that TRIM28 influences the self-renewal and chemotherapy resistance of tumor stem cells via modulating the expression of tumor stem cell markers, including Prominin-1 (CD133) in GBM. Research demonstrates that TRIM28 directly engages with the promoter region of the CD133 gene via an epigenetic mechanism, inhibits histone acetylation (particularly h3k27ac), and therefore downregulates CD133 expression. The knockdown of trim28 might significantly reduce the stem cell properties of GBM cells, hinder tumor sphere formation, and enhance their sensitivity to temozolomide (TMZ). Subsequent study demonstrated that trim28 recruited histone deacetylase (HDAC) and DNA methyltransferase (DNMT) complexes to the CD133 promoter region, leading to localized chromatin compaction and gene silencing. This mechanism depends on the PhD bromo domain of TRIM28, signifying the specificity of its epigenetic regulatory function. Besides, there are also other mechanism that to do with TRIM28 and GBM. As for the therapeutic potential, TRIM28 can be used as a significant biomarker in GBM. Besides, CD133-targeted chimeric antigen receptor T cell may be a viable therapeutic approach to target CD133+ cancer stem cells in human glioblastoma or other treatment-resistant primary malignancies. Nonetheless, the precise mechanism of TRIM in GBM necessitates further investigation.