Downregulation of RND3/RhoE in glioblastoma patients promotes tumorigenesis through augmentation of notch transcriptional complex activity

摘要: Activation of Notch signaling contributes to glioblastoma multiform (GBM) tumorigenesis. However, the molecular mechanism that promotes augmentation during GBM genesis remains largely unknown. Identification new factors regulate is critical for tumor treatment. The expression levels RND3 and its clinical implication were analyzed in patients. as a novel factor was demonstrated vitro by cell experiments vivo xenograft model. We found significantly decreased human glioblastoma. inversely correlated with activity, size, proliferation, positively patient survival time. functioned an endogenous repressor transcriptional complex. physically interacted NICD, CSL, MAML1, complex factors, promoted NICD ubiquitination, facilitated degradation these cofactor proteins. further revealed binding FBW7, ubiquitin ligase, consequently enhanced protein degradation. Therefore, activity inhibited. Forced repressed signaling, which led inhibition proliferation growth mice vivo. Downregulation RND3, however, subsequently glioma proliferation. Inhibition abolished deficiency-mediated conclude downregulation responsible enhancement genesis.