Small trans-membrane and glycosylated protein (SMAGP), a novel small trans-membrane glycoprotein, is reported to be upregulated in multiple cancers and involved in tumor development. However, little is known about its role in the development of glioblastoma (GBM). GEPIA database was used to analyze SMAGP expression and evaluate the prognostic value of SMAGP in GBM. GO and KEGG pathway enrichment analyses were used to predict the biological functions and pathways of SMAGP and 948 SMAGP-correlated genes using DAVID database. Cell viability, colony formation ability, apoptosis, and invasion were evaluated by MTT, colony formation assay, flow cytometry analysis, and Transwell invasion assay, respectively. Western blot was applied to detect the expression of SMAGP, matrix metalloproteinase (MMP)-2, and MMP-9 and analyze the changes of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling. Results showed that SMAGP was upregulated and correlated with poor prognosis in GBM. Functional annotation analysis revealed that SMAGP and 948 SMAGP-correlated genes were primarily associated with cell adhesion and PI3K/Akt pathway. SMAGP interference inhibited cell viability and colony formation ability and promoted apoptosis in GBM cells. Moreover, SMAGP interference inhibited GBM cell invasion and suppressed MMP-2 and MMP-9 expression. Additionally, SMAGP silencing inhibited the PI3K/Akt pathway in GBM cells. Overexpression of Akt abolished the effects of SMAGP knockdown on the malignant phenotypes of GBM cells. In conclusion, SMAGP silencing inhibited the malignant phenotypes of GBM cells by inactivating the PI3K/Akt pathway.
Keywords: Apoptosis; Glioblastoma; Invasion; PI3K/Akt pathway; SMAGP; Viability.
Copyright © 2020 Elsevier Inc. All rights reserved.