PMID- 35461073 OWN - NLM STAT- MEDLINE DCOM- 20220517 LR - 20220531 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 610 DP - 2022 Jun 25 TI - GALNT12 is associated with the malignancy of glioma and promotes glioblastoma multiforme in vitro by activating Akt signaling. PG - 99-106 LID - S0006-291X(22)00575-7 [pii] LID - 10.1016/j.bbrc.2022.04.052 [doi] AB - 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. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Zheng, Yongjia AU - Zheng Y AD - School of Pharmaceutical Sciences, National-Local Joint Engineering Laboratory of Druggability and New Drugs Evaluation, Sun Yat-sen University, Guangzhou, 510006, China. FAU - Liang, Minting AU - Liang M AD - School of Pharmaceutical Sciences, National-Local Joint Engineering Laboratory of Druggability and New Drugs Evaluation, Sun Yat-sen University, Guangzhou, 510006, China. FAU - Wang, Bowen AU - Wang B AD - College of Life Science, Northwest University, Xi'an, 710127, China. FAU - Kang, Li AU - Kang L AD - School of Pharmaceutical Sciences, National-Local Joint Engineering Laboratory of Druggability and New Drugs Evaluation, Sun Yat-sen University, Guangzhou, 510006, China. FAU - Yuan, Yanqiu AU - Yuan Y AD - School of Pharmaceutical Sciences, National-Local Joint Engineering Laboratory of Druggability and New Drugs Evaluation, Sun Yat-sen University, Guangzhou, 510006, China; Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangzhou, 510990, China. FAU - Mao, Yang AU - Mao Y AD - School of Pharmaceutical Sciences, National-Local Joint Engineering Laboratory of Druggability and New Drugs Evaluation, Sun Yat-sen University, Guangzhou, 510006, China; Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangzhou, 510990, China. Electronic address: maoyang3@mail.sysu.edu.cn. FAU - Wang, Shengjun AU - Wang S AD - School of Pharmaceutical Sciences, National-Local Joint Engineering Laboratory of Druggability and New Drugs Evaluation, Sun Yat-sen University, Guangzhou, 510006, China; Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangzhou, 510990, China. Electronic address: wangshj35@mail.sysu.edu.cn. LA - eng PT - Journal Article DEP - 20220414 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - EC 2.4.1.- (GALNT12 protein, human) RN - EC 2.4.1.- (N-Acetylgalactosaminyltransferases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - *Brain Neoplasms/pathology MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Gene Expression Regulation, Neoplastic MH - *Glioblastoma/pathology MH - *Glioma/pathology MH - Humans MH - *N-Acetylgalactosaminyltransferases/genetics/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism OTO - NOTNLM OT - EGF OT - GALNT12 OT - GBM OT - Glioblastoma multiforme OT - O-glycosylation COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/04/24 06:00 MHDA- 2022/05/18 06:00 CRDT- 2022/04/23 20:13 PHST- 2022/04/02 00:00 [received] PHST- 2022/04/11 00:00 [revised] PHST- 2022/04/11 00:00 [accepted] PHST- 2022/04/24 06:00 [pubmed] PHST- 2022/05/18 06:00 [medline] PHST- 2022/04/23 20:13 [entrez] AID - S0006-291X(22)00575-7 [pii] AID - 10.1016/j.bbrc.2022.04.052 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2022 Jun 25;610:99-106. doi: 10.1016/j.bbrc.2022.04.052. Epub 2022 Apr 14.