ELAVL1通过稳定TL1A mRNA促进胃癌的进展和转移

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Tao Jiang , Sihan Bo , Yong You , Yongwei Wang , Lei Hou , Shuang Tian , Bing Bai , Yu Cheng , Yaxian Gao
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引用次数: 0

摘要

ELAVL1样rna结合蛋白1 (ELAVL1)是参与肿瘤进展和转移的关键rna结合蛋白。本研究发现了ELAVL1和TL1A mRNA之间先前未被认识的相互作用,阐明了其通过激活PI3K/Akt信号通路促进胃癌(GC)进展的作用。过表达ELAVL1可显著增强GC细胞的增殖和迁移,而沉默ELAVL1可显著降低这些过程。此外,稳定敲除ELAVL1可显著抑制裸鼠GC细胞来源的异种移植瘤的生长。在机制上,ELAVL1通过其RNA识别基序(RRM1和RRM3)直接与TL1A mRNA结合。TL1A mRNA上的结合位点已经确定在两个区域:一个位于核苷酸1605和1868之间,另一个位于核苷酸4324和4587之间。ELAVL1通过激活下游PI3K/Akt信号通路,稳定TL1A mRNA表达,促进GC进展。我们的研究结果强调了一个涉及ELAVL1、TL1A mRNA和PI3K/Akt的新调控轴,为rna介导的致癌信号传导提供了新的见解,并确立了ELAVL1作为胃癌的潜在治疗靶点。这一发现为开发针对ELAVL1的靶向治疗奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ELAVL1 facilitates gastric cancer progression and metastasis through TL1A mRNA stabilization
ELAV-like RNA-binding protein 1 (ELAVL1) is a key RNA-binding protein involved in tumor progression and metastasis. This study identifies a previously unrecognized interaction between ELAVL1 and TL1A mRNA, elucidating its role in promoting gastric cancer (GC) progression through the activation of the PI3K/Akt signaling pathway. Overexpression of ELAVL1 significantly enhances the proliferation and migration of GC cells, whereas silencing ELAVL1 leads to a marked reduction in these processes. Additionally, stable knockout of ELAVL1 significantly inhibits the growth of xenograft tumors derived from GC cells in nude mice. Mechanistically, ELAVL1 directly binds to TL1A mRNA through its RNA recognition motifs (RRM1 and RRM3). The binding sites on TL1A mRNA have been confirmed in two regions: one located between nucleotides 1605 and 1868, and the other between 4324 and 4587. ELAVL1 stabilizes TL1A mRNA expression and promotes GC progression by activating the downstream PI3K/Akt signaling pathway.Our findings highlight a novel regulatory axis involving ELAVL1, TL1A mRNA, and PI3K/Akt, providing new insights into RNA-mediated oncogenic signaling and establishing ELAVL1 as a potential therapeutic target for GC. This discovery lays the groundwork for developing targeted therapies against ELAVL1.
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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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