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ALKBH5 介导的 circFOXP1 m6A 修饰通过调节 SOX4 表达和海绵吸附 miR-338-3p 促进胃癌进展。

ALKBH5-mediated m6A modification of circFOXP1 promotes gastric cancer progression by regulating SOX4 expression and sponging miR-338-3p.

机构信息

Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China.

出版信息

Commun Biol. 2024 May 14;7(1):565. doi: 10.1038/s42003-024-06274-7.

Abstract

Circular RNAs (circRNAs) have recently been suggested as potential functional modulators of cellular physiology processes in gastric cancer (GC). In this study, we demonstrated that circFOXP1 was more highly expressed in GC tissues. High circFOXP1 expression was positively associated with tumor size, lymph node metastasis, TNM stage, and poor prognosis in patients with GC. Cox multivariate analysis revealed that higher circFOXP1 expression was an independent risk factor for disease-free survival (DFS) and overall survival (OS) in GC patients. Functional studies showed that increased circFOXP1 expression promoted cell proliferation, cell invasion, and cell cycle progression in GC in vitro. In vivo, the knockdown of circFOXP1 inhibited tumor growth. Mechanistically, we observed ALKBH5-mediated m6A modification of circFOXP1 and circFOXP1 promoted GC progression by regulating SOX4 expression and sponging miR-338-3p in GC cells. Thus, our findings highlight that circFOXP1 could serve as a novel diagnostic and prognostic biomarker and potential therapeutic target for GC.

摘要

环状 RNA(circRNAs)最近被认为是胃癌(GC)细胞生理过程的潜在功能调节剂。在这项研究中,我们证明了 circFOXP1 在 GC 组织中表达更高。circFOXP1 高表达与 GC 患者的肿瘤大小、淋巴结转移、TNM 分期和预后不良呈正相关。Cox 多因素分析显示,circFOXP1 高表达是 GC 患者无病生存(DFS)和总生存(OS)的独立危险因素。功能研究表明,circFOXP1 表达增加促进了 GC 细胞的体外增殖、侵袭和细胞周期进程。在体内,circFOXP1 的敲低抑制了肿瘤生长。机制上,我们观察到 ALKBH5 介导的 circFOXP1 的 m6A 修饰,circFOXP1 通过调节 GC 细胞中的 SOX4 表达和海绵 miR-338-3p 促进 GC 进展。因此,我们的研究结果表明,circFOXP1 可以作为 GC 的新型诊断和预后生物标志物以及潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc5b/11094028/6e0a0b72e2ba/42003_2024_6274_Fig1_HTML.jpg

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