RESUMO
Although the tumorigenic potential of glioma stem cells (GSCs) is associated with multiple molecular alterations, the gene amplification status of GSCs has not been elucidated. Overexpression of HomeoboxA5 (HOXA5) is associated with increased glioma malignancy. In this study, we identify the gene amplification and protein overexpression of HOXA5 in GSCs and its function in regulating GSC maintenance and the downstream transcriptional effector, to explore the significance of HOXA5 amplification/overexpression for GSC identification and prognostic determination. The HOXA5 gene is significantly amplified in glioblastoma (GBM) and is an independent prognostic factor for predicting worse patient outcomes. Specifically, HOXA5 gene amplification and the resultant protein overexpression are correlated with increased proportions of GSCs and enhanced self-renewal/invasiveness of these cells. Disruption of HOXA5 expression impairs GSC survival and GBM tumor propagation. Mechanistically, HOXA5 directly binds to the promoter region of protein tyrosine phosphatase receptor type Z1 (PTPRZ1), thereby upregulating this gene for GSC maintenance. Suppression of PTPRZ1 largely compromises the pro-tumoral effect of HOXA5 on GSCs. In summary, HOXA5 amplification serves as a genetic biomarker for predicting worse GBM outcome, by enhancing PTPRZ1-mediated GSC survival.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Neoplasias Encefálicas/patologia , Carcinogênese/metabolismo , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Glioblastoma/patologia , Glioma/patologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Células-Tronco Neoplásicas/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/metabolismoRESUMO
To reveal the controlling mechanism of urban polluted river,four trophic level urban river was studied. The change of distribution of organic matter and nitrogen in the sediment was studied while the organic matter was disposed. High level of organic matter is the significant feature of urban city rivers. the humin (HM) was the major fraction of humus, accounting for more than 65% of OM. The most proportion of the total nitrogen (TN) was organic nitrogen which accounted for more than 50%. The amount of organic matter removal increased after the sediment adsorbed the saturated ammonia, which suggested ammonia as the main limited factor for the decomposition of organic matter. The most of Ammonia was adsorbed onto unstable humins. The HM was more stable than other organic matter which was disposed by Hydrogen peroxide (H2O2).
