Recent studies have unveiled that LINC00173 promotes small cell lung cancer progression. However, LINC00173 has not been studied in Wilms' tumor (WT). N-glycosylation is a complex post-translational protein modification, and alterations of protein glycosylation have been identified to affect the development of multiple tumors, including WT. MGAT1, known as N-acetylglucosaminyltransferase I (GlcNAcT-1), could initiate synthesis of complex N-glycans, but it has never been related to LINC00173 in WT. This study aimed to explore if LINC00173 could impact WT progression via MGAT1. RT-qPCR and western blot were done to measure the expression and protein levels. Functional assays, as well as animal experiments were conducted to evaluate the function of genes in vivo and in vitro. Additionally, RNA pull-down, RIP, and dual-luciferase reporter assays were carried out to determine the molecular bindings. In vitro experiments proved that sh-LINC00173 inhibited WT cell invasion and promoted WT cell apoptosis, while in vivo experiments indicated sh-LINC00173 restrained WT progression. LINC00173 stabilized MGAT1 mRNA by recruiting HNRNPA2B1. Meanwhile, MGAT1 was verified to stabilize MUC3A protein by inducing N-glycosylation. In summary, our study first discovered that LINC00173 promoted WT progression through MGAT1-mediated MUC3A N-glycosylation, giving new clues to further understanding the mechanism underlying WT progression.
Keywords: LINC00173; MGAT1; MUC3A; N-glycosylation; Wilms’ tumor; mRNA stability.