9/7/2023 0 Comments Merck millipore sigma aldrichOur previous study showed that long-term treatment with TMZ caused the acquired resistance derived from the enrichment of the TIC’s properties by increasing superoxide dismutase 2 (SOD2) accompanied with CD133 up-regulation. Accumulating studies have demonstrated that CD133 is a valuable TICs marker to predict the recurrence of high-grade glioma. This specific subgroup of cells is characterized by self-renewal and multipotency, referred to as stem cell properties. Studies indicate that TICs are responsible for drug-acquired resistance. Īpart from MGMT leading to TMZ resistance, tumor-initiating cells (TICs) in gliomas may be involved in the resistance. The cells express O6-methylguanine-DNA methyltransferase (MGMT), allowing them to escape drug cytotoxicity. Therefore, understanding its mechanism would significantly contribute to the therapeutic benefits. However, most patients experience tumor recurrence, and the mechanism of TMZ resistance is complicated as multiple factors are involved in it. Despite the outcomes, a first-line chemotherapeutic drug, temozolomide (TMZ), is considered to control disease by inducing lethal DNA damage. Glioblastoma (GBM) is a fatal disease with bad outcomes, and the prognosis has not improved even with advanced treatment. Our findings on the effects of SH3GLB1 on the cells will help explain tumor resistance formation. These data indicate that SH3GLB1 can regulate CD133 expression, suggesting that the protein plays a crucial role in TICs. The H4K5 acetylation of the CD133 promoter was later suggested to be the mediating mechanism of SH3GLB1. Inhibition of SH3GLB1 attenuated frequency and size of spheroid formation, and the levels of CD133 and histone 4 lysine 5 (H4K5) acetylation can be simultaneously regulated by SH3GLB1 modification. The CD133 + cells from resistant cells with enhanced SH3GLB1 levels more easily survived cytotoxic treatment than those from the parental cells. Finally, in vitro transcription assays were used to validate the association between SH3GLB1 and CD133. Then RNA interference was applied to observe the effects of the target protein on TIC-related features. The parental, the derived resistant cell lines and their CD133 + cells were used, and the levels of the proteins were compared by western blotting. Therefore, we propose that SH3GLB1 participate in the impact on tumor-initiating cells (TICs). We found that SH3GLB1 is a crucial factor for cells to evade temozolomide (TMZ) cytotoxicity through autophagy-mediated oxidative phosphorylation, which is associated with CD133 levels. Glioblastoma (GBM), a malignant brain tumor, has poor survival outcomes due to recurrence or drug resistance.
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