There is some evidence supporting an association between Cullin-5 (CUL5) and cancer, but no research using pan-cancer analysis has been conducted previously. We therefore investigated the oncogenic role of CUL5 in 33 tumors from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Many cancers reduce CUL5 levels, and the prognosis of certain cancers is vitally linked with CUL5 expression. CUL5 expression is associated with CD8 + T-cell infiltration levels in uveal melanomas and head and neck squamous cell carcinomas, and we observed a positive relationship between CUL5 and Tcm (T central memory) cells, and a negative relationship between T helper (Th) cells and pDC (plasmacytoid DC). CUL5 had negative associations with NK cells, NK CD56
bright
cells, NK CD56
dim
cells, Tregs, cytotoxic cells, and Th17 cells. Functions relating to protein processing and ubiquitin were included in the CUL5 functional mechanisms. The top 100 genes that are most strongly related to CUL5 were identified, and enrichment analysis indicated that the biological process with the closest relationship was neddylation, related pathways included the TGF-beta signaling pathway and intracellular receptor signaling pathway. CUL5 is related to biological cell behaviors such as chromosome segregation and positive regulation of chromosome organization. As the first study to perform a pan-cancer analysis of CUL5, the present findings will improve the understanding of the oncogenic role of CUL5 in different tumors.
Glioblastoma (GBM) is the most lethal malignant tumor in the central nervous system, with a median survival of only 14 months. Cholesterol, which is the main component of cell membrane and the precursor of many hormones, is one of the most important lipid components in human body. Since reprogramming of the cholesterol metabolic profile has been discovered in many cancers including GBM, cholesterol metabolism becomes a promising potential target for therapy. Since GBM cells rely on external cholesterol to survive and accumulate lipid droplets to meet their rapid growth needs, targeting the metabolism of cholesterol by different strategies including inhibition of cholesterol uptake and promotion of cholesterol efflux by activating LXRs and disruption of cellular cholesterol trafficking, inhibition of SREBP signaling, inhibition of cholesterol esterification, could potentially oppose the growth of glial tumors. In this review, we discussed the above findings and describe cholesterol synthesis and homeostatic feedback pathways in normal brain tissues and brain tumors, statin use in GBM and the role of lipid rafts and cholesterol precursors and oxysterols in the treatment and pathogenesis of GBM are also summarized.
The cystine/glutamate antiporter xCT (SLC7A11) is frequently upregulated in many cancers, including glioblastoma (GBM). SLC7A11-mediated cystine taken up is reduced to cysteine, a precursor amino acid for glutathione synthesis and antioxidant cellular defe nse. However, little is known about the biological functions of SLC7A11 and its effect on therapeut ic response in GBM.Here, we report that the expression of SLC7A11 is higher in GBM compared with normal brain tissue, but is negatively associated with tumor grades and positively impacts survival in the bioinformatic analysis of TCGA and CGGA database. Additionally, a negative association between SLC7A11 and mismatch repair (MMR) gene expression was identified by Pearson correlation analysis. In the GBM cells with glucose-limited culture conditions, overexpression of SLC7A11 significantly decreased MMR gene expression, including MLH1, MSH6, and EXO1. SLC7A11-overexpressed GBM cells demonstrated elevated double-strand break (DSB) levels and increased sensitivity to radiation treatment. Taken together, our work indicates that SLC7A11 might be a potential biomarker for predicting a better response to radiotherapy in GBM.
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