2. Academic Validation
  3. GALNT14-mediated O-glycosylation drives lung adenocarcinoma progression by reducing endogenous reactive oxygen species generation

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

  • Cell Signal. 2024 Dec:124:111477. doi: 10.1016/j.cellsig.2024.111477.
Bingbing Tang 1,  Kelong Wang 2,  Qiulei Ren 3,  Junshuo Zhou 3,  Yuewen Xu 3,  Liaoyuan Liu 3,  Bin Yin 3,  Yaling Zhang 3,  Qian Huang 3,  Ruiqi Lv 3,  Zhiguo Luo 4,  Hongyan Zhao 5,  Li Shen 6
Affiliations

Affiliations

  • 1 Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China; Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, Hubei, China.
  • 2 Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China; Key Laboratory of Cancer Therapy Resistance and Clinical Translational Study, Shiyan 442000, Hubei, China.
  • 3 Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, Hubei, China.
  • 4 Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China; Key Laboratory of Cancer Therapy Resistance and Clinical Translational Study, Shiyan 442000, Hubei, China. Electronic address: zhiguo_luo@163.com.
  • 5 Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, Hubei, China. Electronic address: zhyzhy62@163.com.
  • 6 Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China; Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, Hubei, China; Key Laboratory of Cancer Therapy Resistance and Clinical Translational Study, Shiyan 442000, Hubei, China. Electronic address: shenli_suda@163.com.
PMID: 39426495 DOI: 10.1016/j.cellsig.2024.111477
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.

Keywords

GALNT14; Glycosylation; LUAD; Progression; ROS.

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