YTHDF2通过不依赖m6A修饰而上调PPP2CA在胃癌中发挥抑瘤作用。

IF 3.7 3区生物学 Q1 BIOCHEMICAL RESEARCH METHODS Biological Procedures Online Pub Date : 2023-03-04 DOI:10.1186/s12575-023-00195-1

Ying Zhou, Kailing Fan, Ning Dou, Li Li, Jialin Wang, Jingde Chen, Yandong Li, Yong Gao

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引用次数: 1

摘要

背景:YTHDF2是RNA上n6 -甲基腺苷(m6A)修饰的重要读者之一。越来越多的证据表明，YTHDF2在不同癌症的肿瘤发生和转移调控中发挥着不可或缺的作用，但其在胃癌中的生物学功能和潜在机制尚不清楚。目的:探讨YTHDF2在胃癌中的临床意义及生物学功能。结果:与匹配的正常胃组织相比，胃癌组织中YTHDF2的表达明显降低。YTHDF2表达水平与胃癌患者肿瘤大小、AJCC分型及预后呈负相关。在功能上，YTHDF2的减少促进了胃癌细胞在体外和体内的生长和迁移，而YTHDF2的过表达则表现出相反的表型。在机制上，YTHDF2以不依赖m6a的方式增强PP2A(蛋白磷酸酶2A)的催化亚基PPP2CA的表达，而沉默PPP2CA可拮抗GC细胞中YTHDF2过表达引起的抗肿瘤作用。结论:这些研究结果表明，YTHDF2在胃癌中下调，其下调可能通过PPP2CA表达的机制促进胃癌的进展，提示YTHDF2可能是一种有希望的胃癌诊断生物标志物和尚未发现的治疗靶点。

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YTHDF2 exerts tumor-suppressor roles in gastric cancer via up-regulating PPP2CA independently of m⁶A modification.

Background: YTHDF2 is one of important readers of N6-methyladenosine (m⁶A) modification on RNA. Growing evidence implicates that YTHDF2 takes an indispensable part in the regulation of tumorigenesis and metastasis in different cancers, but its biological functions and underlying mechanisms remain elusive in gastric cancer (GC).

Aim: To investigate the clinical relevance and biological function of YTHDF2 in GC.

Results: Compared with matched normal stomach tissues, YTHDF2 expression was markedly decreased in gastric cancer tissues. The expression level of YTHDF2 was inversely associated with gastric cancer patients' tumor size, AJCC classification and prognosis. Functionally, YTHDF2 reduction facilitated gastric cancer cell growth and migration in vitro and in vivo, whereas YTHDF2 overexpression exhibited opposite phenotypes. Mechanistically, YTHDF2 enhanced expression of PPP2CA, the catalytic subunit of PP2A (Protein phosphatase 2A), in an m⁶A-independent manner, and silencing of PPP2CA antagonized the anti-tumor effects caused by overexpression of YTHDF2 in GC cells.

Conclusion: These findings demonstrate that YTHDF2 is down-regulated in GC and its down-regulation promotes GC progression via a possible mechanism involving PPP2CA expression, suggesting that YTHDF2 may be a hopeful biomarker for diagnosis and an unrevealed treatment target for GC.

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来源期刊

Biological Procedures Online 生物-生化研究方法

CiteScore

10.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： iological Procedures Online publishes articles that improve access to techniques and methods in the medical and biological sciences. We are also interested in short but important research discoveries, such as new animal disease models. Topics of interest include, but are not limited to: Reports of new research techniques and applications of existing techniques Technical analyses of research techniques and published reports Validity analyses of research methods and approaches to judging the validity of research reports Application of common research methods Reviews of existing techniques Novel/important product information Biological Procedures Online places emphasis on multidisciplinary approaches that integrate methodologies from medicine, biology, chemistry, imaging, engineering, bioinformatics, computer science, and systems analysis.