1. BUB1 potentiates gastric cancer proliferation and metastasis by activating TRAF6/NF-κB/FGF18 through m6A modification.
- Author
-
Wang K, Shen K, Wang J, Yang K, Zhu J, Chen Y, Liu X, He Y, Zhu X, Zhan Q, Shi T, and Li R
- Subjects
- Humans, Animals, Mice, Cell Line, Tumor, Protein Serine-Threonine Kinases metabolism, Protein Serine-Threonine Kinases genetics, Mice, Inbred BALB C, Gene Expression Regulation, Neoplastic, Cell Movement, Male, Female, Neoplasm Metastasis, Adenosine analogs & derivatives, Adenosine metabolism, Methyltransferases metabolism, Methyltransferases genetics, Prognosis, Stomach Neoplasms pathology, Stomach Neoplasms metabolism, Stomach Neoplasms genetics, Cell Proliferation, NF-kappa B metabolism, Mice, Nude, Fibroblast Growth Factors metabolism, Fibroblast Growth Factors genetics
- Abstract
Aims: Gastric cancer (GC) is one of the most common malignant tumors of the digestive system. High expression of the mitotic kinase BUB1 has been shown to be associated with the development of many cancers, but the role of BUB1 in GC is still unclear. The current study aimed to investigate the role of BUB1 in GC., Materials and Methods: BUB1 inhibitor, siRNA or BUB1 overexpression plasmid-mediated functional studies were performed in vitro and in vivo to explore the oncogenic role of BUB1 in GC. The expression of BUB1 and FGF18 in GC tumor samples was determined by IHC staining. RNA-seq, Western blot, MeRIP-qPCR and Co-IP assays were used to investigate the molecular mechanisms by which BUB1 regulates GC progression., Key Findings: Knockdown of BUB1 significantly inhibited the proliferation and metastasis of GC cells in vitro and in vivo. Moreover, overexpression of BUB1 significantly promoted the proliferation, migration and invasion of GC cells. High expression of BUB1 and FGF18 in GC tissues predicted poor prognosis in GC patients. Mechanistically, BUB1 interacted with METTL3 and induced m6A modification of TRAF6 mRNA, further activating the NF-κB/FGF18 axis in GC cells., Significance: Our results confirmed that BUB1 acts as a positive regulator of GC cell proliferation and metastasis by activating the TRAF6/NF-κB/FGF18 pathway through METTL3-mediated m6A methylation. Targeting the BUB1/METTL3/TRAF6/NF-κB/FGF18 axis might be a novel diagnostic and therapeutic strategy in GC., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF