LINC00173 Promotes Wilms’ Tumor Progression Through MGAT1-mediated MUC3A N-glycosylation

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 function of genes <i>in vivo</i> and <i>in vitro</i>. Additionally, RNA pull-down, RIP, and dual luciferase reporter assays were carried out to determine the molecular bindings. <i>In vitro</i> experiments proved that sh-LINC00173 inhibited WT cell invasion and promoted WT cell apoptosis, while <i>in vivo</i> 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.