Xianlei Cai , Xueying Li , Miaozun Zhang , Zhebin Dong , Yihui Weng , Weiming Yu
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引用次数: 0
Abstract
N6-methyladenosine (m6A) and lipid metabolism reprogramming play pivotal roles in cancer development. Nevertheless, the precise functions of m6A methyltransferase RNA Binding Motif Protein 15 (RBM15) and its interactions with ATP Citrate Lyase (ACLY) in gastric cancer (GC) have not been fully elucidated. In this study, we comprehensively investigate the biological roles and potential mechanisms of RBM15 and ACLY in GC. We employed a combination of fundamental experiments and bioinformatics analyses to unravel the enigmatic roles of RBM15 and ACLY. The expression of RBM15 was evaluated. The biological roles of RBM15 in GC cells were investigated through in vitro and in vivo studies. ACLY was selected as the candidate target of RBM15. Subsequently, to decipher the underlying mechanisms of the RBM15/ACLY axis, we conducted a series of experiments including methylated RNA immunoprecipitation qPCR, dual-luciferase reporter assays, and RNA immunoprecipitation qPCR. We observed a conspicuous upregulation of RBM15 in GC, and its heightened expression was associated with an unfavorable prognosis. Functionally, RBM15 fostered the proliferation and invasiveness of GC cells both in vitro and in vivo. Mechanistically, ACLY emerged as the downstream target of RBM15 and it was validated as an oncogene in GC cells. RBM15 mediated the activation of ACLY by regulating m6A modification in an IGF2BP2-dependent manner, thereby driving lipogenesis and exacerbating the malignant characteristics in GC. The activation of ACLY, facilitated by RBM15/IGF2BP2-mediated m6A modification, drives lipogenesis and promotes the progression of GC.
期刊介绍:
BBA Molecular and Cell Biology of Lipids publishes papers on original research dealing with novel aspects of molecular genetics related to the lipidome, the biosynthesis of lipids, the role of lipids in cells and whole organisms, the regulation of lipid metabolism and function, and lipidomics in all organisms. Manuscripts should significantly advance the understanding of the molecular mechanisms underlying biological processes in which lipids are involved. Papers detailing novel methodology must report significant biochemical, molecular, or functional insight in the area of lipids.