GALNT14-mediated O-glycosylation drives lung adenocarcinoma progression by reducing endogenous reactive oxygen species generation

Abstract

Aberrant glycosylation, resulting from dysregulated expression of glycosyltransferases, is a prevalent feature of cancer cells. N-acetylgalactosaminyltransferase-14 (GALNT14) serves as a pivotal enzyme responsible for initiating O-GalNAcylation. It remains unclear whether and how GALNT14 affects lung adenocarcinoma (LUAD). Here, GALNT14 expression in LUAD was analyzed by searching public databases and verified by examining clinical samples. Bioinformatics, LC-MS/MS, RNA-seq, and RIP-seq analyses were used to uncover the mechanism underlying GALNT14. We observed that GALNT14 was frequently overexpressed in LUAD tissues. High GALNT14 expression was positively associated with advanced TNM stage, larger tumor size, and unfavorable prognosis. Functionally, GALNT14 facilitated LUAD cell proliferation, migration, and invasion in vitro and accelerated tumor growth in vivo. Mechanistically, GALNT14 reduced the accumulation of endogenous reactive oxygen species (ROS) to exert its oncogenic function via O-glycosylating hnRNPUL1 to upregulate AKR1C2 expression. Meanwhile, GALNT14 expression was directly modulated by miR-125a.These findings indicated that GALNT14-mediated O-GalNAcylation could drive LUAD progression via eliminating ROS and might be a valuable therapeutic target.