O-GlcNAc transferase promotes glioblastoma through genes responsible for cell survival, invasion and inflammation

Metabolic reprogramming has emerged as one of the key hallmarks of cancer cells. Various metabolic pathways are dysregulated in cancers including hexosamine biosynthesis pathway (HBP). Protein O-GlcNAcylation catalyzed by O-GlcNAc transferase (OGT), the effector of HBP is found to be upregulated in most cancers. Post-translational O-GlcNAcylation of various signaling and transcriptional regulators could promote cancer cell maintenance and progression through protein stability and gene expression regulation. Indeed, among majority of O-GlcNAcylated proteins are gene specific transcription factors and chromatin regulators. Therefore, investigating the role of OGT in particular types of cancers is crucial. Here, we have investigated the role of OGT in glioblastoma. OGT knockdown and chemical inhibition led to reduced glioblastoma cell proliferation and downregulation of many genes known to play key roles in glioblastoma cell proliferation, migration and invasion.We knocked down OGT and OGA enzyme expression by shRNAs followed by RNA sequencing was carried. Total RNA was isolated using MasterPure RNA isolation Kit. Ribosomal RNA was depleted. Libraries were prepared using NEBNext Ultra II RNA Library Prep Kit