GALNT12 is associated with the malignancy of glioma and promotes glioblastoma multiforme in vitro by activating Akt signaling

• Published in: Biochemical and biophysical research communications 2022-06, Vol.610, p.99-106
• Main Authors: Zheng, Yongjia, Liang, Minting, Wang, Bowen, Kang, Li, Yuan, Yanqiu, Mao, Yang, Wang, Shengjun
• Format: Article
• Language: English
• Subjects: Brain Neoplasms - pathology; Cell Line, Tumor; Cell Proliferation - genetics; EGF; GALNT12; GBM; Gene Expression Regulation, Neoplastic; Glioblastoma - pathology; Glioblastoma multiforme; Glioma - pathology; Humans; N-Acetylgalactosaminyltransferases - genetics; N-Acetylgalactosaminyltransferases - metabolism; O-glycosylation; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.04.052

Abnormal expression of mucin-type O-glycosylation has been reported to be associated with a variety of human cancers including gliomas. However, little is known about its contribution to the malignancy of Glioblastoma Multiforme (GBM), the deadliest form of brain tumors. Here, we conducted a detailed analysis of the expression profiles of GALNT gene family, which encode polypeptide-N-acetyl-galactosaminyltransferases (GalNAc-Ts) and are responsible for initiating O-glycans, both in the Cancer Genome Atlas (TCGA) and in the Chinese Glioma Genome Atlas (CGGA) databases. We discovered that GALNT12 is the only member within the GALNT family, whose expression demonstrated significant correlation with a worse prognosis of GBM. Genetic knockdown (KD) and knockout (KO) of GALNT12 in U87 MG, a representative GBM cell line with high GALNT12 expression, confirmed that GALNT12 deficiency leads to decreased cell proliferation, migration and invasion. Mechanism study revealed that GALNT12 KD and KO decreased the level of epidermal growth factor (EGF) and consequently attenuated Akt signaling within the cell. In summary, our results indicated that GALNT12 facilitates the malignant characteristics of GBM by influencing the PI3K/Akt/mTOR axis and may serve as a novel prognosis biomarker and a potential therapeutic target of GBM. •GALNT12 expression significantly correlates with poor prognosis in GBM patients.•Downregulation of GALNT12 leads to decreased proliferation, migration and invasion of GBM cells.•EGF expression and PI3K/Akt signaling pathway are modulated by GALNT12 in GBM cell lines.