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 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.

CircAKT1 acts as a sponge of miR-338-3p to facilitate clear cell renal cell carcinoma progression by up-regulating CAV1.

Circular RNAs (CircRNAs) have become a research focus for their important implication in tumorigenesis and cancer progression. This study intends to observe the function of circAKT1 in clear cell renal cell carcinoma (ccRCC) and its underlying molecular mechanism. In the present study, we confirmed the up-regulation of circAKT1 in ccRCC tissues and cells. High circAKT1 expression was positively associated with TNM stage, lymph node metastasis and predicted an adverse prognosis. Functionally, knockdown of circAKT1 suppressed cell proliferation, colony formation, migration, invasion and EMT in vitro. Mechanistic analysis uncovered that circAKT1 could act as a sponge for miR-338-3p to prevent the degradation of caveolin-1 (CAV1). Interestingly, the anti-neoplastic effect of circAKT1 knockdown on ccRCC was abated due to miR-338-3p down-regulation or CAV1 overexpression. To summarize, circAKT1 facilitated ccRCC progression at least partly by sequestering miR-338-3p to up-regulate CAV1 expression. Our findings raised the possibility of exploiting circAKT1 as a potential prognostic biomarker and therapeutic target in ccRCC.