Chien, Chia-Hung; Yang, Wen-Bin; Chuang, Jian-Ying; Lee, Jung-Shun; Liao, Wei-An; Huang, Chih-Yuan; Chen, Pin-Yuan; Wu, An-Chih; Yang, Shun-Tai; Lai, Chien-Cheng; Chi, Pei-I.; Chu, Jui-Mei; Cheng, Siao Muk; Liu, Chan-Chuan; Hwang, Daw-Yang; Chen, Shang-Hung; Chang, Kwang-Yu published the artcile< SH3GLB1-related autophagy mediates mitochondrial metabolism to acquire resistance against temozolomide in glioblastoma>, Related Products of 112-63-0, the main research area is temozolomide SH3GLB1 autophagy mitochondrial metabolism glioblastoma; Autophagy; Mitochondrial functions; Resistance; SH3GLB1; Temozolomide.
The mechanism by which glioblastoma evades temozolomide (TMZ)-induced cytotoxicity is largely unknown. We hypothesized that mitochondria plays a role in this process. RNA transcriptomes were obtained from tumor samples and online databases. Expression of different proteins was manipulated using RNA interference or gene amplification. Autophagic activity and mitochondrial metabolism was assessed in vitro using the resp. cellular and mol. assays. In vivo anal. were also carried out in this study. High SH3GLB1 gene expression was found to be associated with higher disease grading and worse survival profiles. Single-cell transcriptome anal. of clin. samples suggested that SH3GLB1 and the altered gene levels of oxidative phosphorylation (OXPHOS) were related to subsets expressing a tumor-initiating cell signature. The SH3GLB1 protein was regulated by promoter binding with Sp1, a factor associated with TMZ resistance. Downregulation of SH3GLB1 resulted in retention of TMZ susceptibility, upregulated p62, and reduced LC3B-II. Autophagy inhibition by SH3GLB1 deficiency and chloroquine resulted in attenuated OXPHOS expression. Inhibition of SH3GLB1 in resistant cells resulted in alleviation of TMZ-enhanced mitochondrial metabolic function, such as mitochondrial membrane potential, mitochondrial respiration, and ATP production SH3GLB1 modulation could determine tumor susceptibility to TMZ. Finally, in animal models, resistant tumor cells with SH3GLB1 knockdown became resensitized to the anti-tumor effect of TMZ, including the suppression of TMZ-induced autophagy and OXPHOS. SH3GLB1 promotes TMZ resistance via autophagy to alter mitochondrial function. Characterizing SH3GLB1 in glioblastoma may help develop new therapeutic strategies against this disease in the future.
Journal of Experimental & Clinical Cancer Research published new progress about ADP/ATP translocase ANT2 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Related Products of 112-63-0.
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