RBM15通过调控ACLY mRNA的N6-甲基腺苷修饰,以IGF2BP2依赖性方式促进胃癌的脂肪生成和恶性程度。

IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xianlei Cai , Xueying Li , Miaozun Zhang , Zhebin Dong , Yihui Weng , Weiming Yu
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引用次数: 0

摘要

N6-甲基腺苷(m6A)和脂质代谢重编程在癌症发展中起着关键作用。然而,m6A甲基转移酶RNA结合动因蛋白15(RBM15)在胃癌(GC)中的确切功能及其与ATP柠檬酸溶酶(ACLY)的相互作用尚未完全阐明。本研究全面探讨了 RBM15 和 ACLY 在胃癌中的生物学作用和潜在机制。我们采用了基础实验和生物信息学分析相结合的方法来揭示 RBM15 和 ACLY 的神秘作用。我们评估了 RBM15 的表达。通过体外和体内研究探讨了 RBM15 在 GC 细胞中的生物学作用。ACLY 被选为 RBM15 的候选靶点。随后,为了破译 RBM15/ACLY 轴的内在机制,我们进行了一系列实验,包括甲基化 RNA 免疫沉淀 qPCR、双荧光素酶报告实验和 RNA 免疫沉淀 qPCR。我们观察到 RBM15 在 GC 中明显上调,其表达的增加与预后不良有关。从功能上看,RBM15在体外和体内都促进了GC细胞的增殖和侵袭性。从机理上讲,ACLY 是 RBM15 的下游靶标,并被证实是 GC 细胞中的致癌基因。RBM15 以一种依赖 IGF2BP2 的方式通过调节 m6A 修饰来介导 ACLY 的活化,从而驱动脂肪生成并加剧 GC 的恶性特征。RBM15/IGF2BP2介导的m6A修饰促进了ACLY的活化,推动了脂肪生成并促进了GC的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
RBM15 promotes lipogenesis and malignancy in gastric cancer by regulating N6-Methyladenosine modification of ACLY mRNA in an IGF2BP2-dependent manner
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.
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来源期刊
CiteScore
11.00
自引率
2.10%
发文量
109
审稿时长
53 days
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.
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