KHDRBS3 facilitates self-renewal and temozolomide resistance of glioblastoma cell lines

        Glioblastoma is a highly aggressive and fatal tumor characterized by the presence of glioblastoma stem cells (GSCs), which contribute significantly to tumor recurrence and resistance to standard therapies, such as temozolomide (TMZ). In this study, subcellular proteomics was employed to identify proteins overexpressed in glioblastoma stem-like cells (GSCs) derived from the U251 cell line. Among the proteins identified, KH RNA Binding Domain Containing, Signal Transduction Associated 3 (KHDRBS3) was found to be upregulated in the GSC population relative to its differentiated derivatives.

        Functional assays revealed that silencing KHDRBS3 expression via RNA interference led to a reduction in GSC proliferation, neurosphere formation, and migration, as well as downregulation of key genes associated with glioblastoma stemness. Notably, the depletion of KHDRBS3 also increased the sensitivity of these cells to TMZ treatment.

        In conclusion, our findings suggest that KHDRBS3 is crucial for maintaining the self-renewal capacity of glioblastoma stem-like cells and contributes to resistance to TMZ. Targeting KHDRBS3 could represent a promising therapeutic strategy to specifically eliminate glioblastoma stem-like cells and potentially enhance the efficacy of existing treatment regimens.