A80-2-02 Fut3 Facilitates Glucose Metabolism of Lung Adenocarcinoma via Activation of Nf-κB Pathway

Abstract Rationale Fucosyltransferases (FUTs) molecules have been identified to be involved in carcinogenesis of malignant tumors. Nevertheless, the biological function of fucosyltransferases-3 (FUT3) in lung adenocarcinoma (LUAD) malignant phenotype remains unclear. Herein, we investigated the association between FUT3 and LUAD pathological process. Methods Immunochemistry, RT-qPCR and western blot assays were conducted to evaluate the expression of FUT3 in LUAD and corresponding adjacent tissues. The prognostic value of FUT3 was assessed via Kaplan-Meier plotter database. The biological process and potential mechanism of FUT3 in LUAD were conducted via GSEA. Additionally, immunofluorescence and metabolite activity detection were performed to determine the potential role of FUT3 in LUAD glucose metabolism. The active biomarkers associated with NF-κB signaling pathway were detected via western blot. Subcutaneous tumor model was conducted to analyze the effect of FUT3 on tumorigenesis of LUAD. Results FUT3 was remarkably upregulated in LUAD tissues compared with adjacent tissues from individuals. FUT3 overexpression may predict poor prognosis of LUAD patients. Knockdown of FUT3 significantly inhibited tumor proliferation, migration and glucometabolic alteration in LUAD cells. Moreover, GSEA demonstrated that elevated FUT3 was positively related to NF-κB signaling pathway. Additionally, in vitro and in vivo assays also indicated that downregulation of FUT3 resulted in the suppression of oncogenesis and glucose metabolism via inactivation of NF-κB pathway. Conclusion Our findings demonstrated that FUT3 was involved in glucometabolic process and tumorigenesis of LUAD via NF-κB signaling pathway. FUT3 may be an optimal target for diagnosis and treatment of LUAD patients. This abstract is funded by: This work was supported by Quanzhou High Level Talent Project (2020C001R), Fujian Respiratory Medicine Center Talent Training Project (HXZX202201), and Startup Fund for Scientific Research, Fujian Medical University (Grant number: 2019QH2039)