ASPM promotes glioblastoma growth by regulating G1 restriction point progression and Wnt-β-catenin signaling

Abstract

Increasing evidence has indicated that the disorganized expression of certain genes promotes tumour progression. In this study, we elucidate the potential key differentially expressed genes (DEGs) between glioblastoma (GBM) and normal brain tissue by analysing three different mRNA expression profiles downloaded from the Gene Expression Omnibus (GEO) database. DEGs were sorted, and key candidate genes and signalling pathway enrichments were analysed. In our analysis, the highest fold change DEG was found to be abnormal spindle-like microcephaly associated (ASPM). The ASPM expression pattern from the database showed that it is highly expressed in GBM tissue, and patients with high expression of ASPM have a poor prognosis. Moreover, ASPM showed aberrantly high expression in GBM cell lines. Loss-of-function assay indicated that ASPM enhances tumorigenesis in GBM cells in vitro. Xenograft growth verified the oncogenic activity of ASPM in vivo. Furthermore, downregulation of ASPM could arrest the cell cycle of GBM cells at the G0/G1 phase and attenuate the Wnt/β-catenin signalling activity in GBM. These data suggest that ASPM may serve as a new target for the therapeutic treatment of GBM.

Transcriptomic Response of Breast Cancer Cells MDA-MB-231 to Docosahexaenoic Acid: Downregulation of Lipid and Cholesterol Metabolism Genes and Upregulation of Genes of the Pro-Apoptotic ER-Stress Pathway

“…The INSIG1 metabolic regulator, whose expression is downregulated in DHA-treated cells (see above), may also play a regulatory role during the G0/G1 transition of cell growth [69]. Genes that are involved in the mitotic process, such as ASPM and SAPCD2 may also play a role in the positive regulation of cell proliferation, and tumor cell growth [70][71][72][73][74], the DHA-induced decrease of their expression is then consistent with the antiproliferative effect of DHA.…”

The Role of Network Science in Glioblastoma

“…Shortly after, ASPM was associated with glioma grade, showing increased expression from non-tumoral samples to grade II, III, and IV gliomas [ 52 , 53 ]. More recently, ASPM was also associated with the survival of patients with GBM [ 50 , 54 ] and glioma [ 55 ], indicating that the hub genes identified by Horvath et al. (2006) [ 50 ] might be new prognostic biomarkers.…”

“…Interestingly, ASPM was previously identified to be expressed at higher levels in secondary GBMs as compared to lower grade astrocytomas [ 56 ] and was further validated in another study as one of the six genes with the highest relative expression in GBM compared to pilocytic astrocytomas [ 57 ]. ASPM also emerged as a hub gene in additional screening studies in GBM [ 55 , 58 , 59 ], and its functional relevance was recently validated in vitro and in vivo [ 55 ]. Specifically, ASPM -silenced GBM cells presented decreased proliferation rates and formed in vivo subcutaneous tumors with significantly reduced sizes.…”

“…Specifically, ASPM -silenced GBM cells presented decreased proliferation rates and formed in vivo subcutaneous tumors with significantly reduced sizes. Mechanistic assays suggested an association between ASPM and the Wnt/ -catenin pathway, highly relevant in GBM, and that ASPM knockdown was linked to a G0/G1 arrest of GBM cells [ 55 ]. Globally, this is a paradigmatic example on the use of network analysis that allowed the identification of a novel GBM biomarker, with critical oncogenic functions and prognostic clinical potential, for which novel smart therapies can be developed in the future.…”

Bioinformatics Identification of Prognostic Factors Associated with Breast Cancer

“…ASPM plays a role in the regulation of mitotic spindle, with a priority role in regulating neurogenesis. Overexpression of ASPM links with tumor progression and poor prognosis in various tumors, including breast cancer [35].Furthermore, it has been reported that ASPM promotes tumor development by regulating Wnt-β-catenin signaling [36,37].…”