ZIC1 inhibits the growth of glioblastoma cell U87MG by enhancing CUL5 expression

Abstract

Abstract ZIC family member 1 (ZIC1) encodes a zinc finger transcription factor 5 which exhibits anti-tumorigenic effects in several cancers. Nevertheless, the mechanism of action in the occurrence of human glioblastoma has been poorly elucidated. Herein, our results demonstrate that ZIC1 inhibits the growth of glioblastoma cell U87MG. Obviously, ZIC1 effects on transcriptome in U87MG, mainly involving in some genes transcriptional ability, e.g.CUL5, DDX10.,HK2, COL6A1, VEGFA, Loxl2, IGFBP3, FOXN3, MT1X, ENO2, TGFB1, PPFIA4,etc..On the other hand, ZIC1 affects proteome in U87MG. For examples, ZIC1 up-regulates CUL5, STIP1, DPP3, PSAT1, SF3A3, MTAP, ERO1A, P4HA2, Serpine1 and down-regulates IFI16, IGF2BP3, ASPH, RAB3B, MARCKS. Furthermore, ZIC1 effects on several signaling pathway in U87MG, including p53 signaling pathway, apoptosis signaling pathway, PI3K-Akt signaling pathway, Hippo signaling pathway, Ras signaling pathway,etc.. Striking, it is worth mentioning that ZIC1 triggers the formation of the fusion genes ,e.g.CDH13-HSD17B2, PPP1R13L-ZNF541. Importantly, ZIC1 enhances CUL5 expression and CUL5 knockdown abrogates the suppressor functions of ZIC1 in U87MG. In conclusions, these results of this first study provide strong evidence for the diagnosis and treatment of human glioblastoma.