YTHDF3 Promoted Gastric Cancer Progression by Facilitating m⁶A-Dependent Degradation of APC mRNA.

IF 2.5 4区医学 Q3 CELL BIOLOGY

Analytical Cellular Pathology Pub Date : 2026-01-01 DOI:10.1155/ancp/5045743

Cao Zhang, Jun Wen, Zijian Liu, Ruyi Li, Yaqin He

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引用次数: 0

Abstract

Background: Stomach adenocarcinoma (STAD) is a highly prevalent malignancy. YTH domain family protein 3 (YTHDF3), an m⁶A reader, correlates with worse survival outcomes in STAD. The aim was to study the impact of YTHDF3 on STAD cells and its underlying regulatory mechanisms.

Methods: Epidemiologically, the GEPIA and Kaplan-Meier Plotter databases were used to examine YTHDF3 expression in STAD and to assess its association with prognosis, with poor prognosis defined by overall survival (OS). Clinical parameters were also analyzed to validate the prognostic value of YTHDF3. Experimentally, STAD patients were selected as the study objects. Immunofluorescence was used to confirm YTHDF3 expression in STAD tissues. In vitro assays examined YTHDF3/Adenomatous polyposis coli (APC) regulation of Wnt signaling.

Results: Epidemiologically, YTHDF3 elevation in STAD (p < 0.05) predicted poorer OS (hazard ratio [HR] = 1.46, 95% confidence interval [95% CI]: 1.17-1.81, p = 0.00066). High YTHDF3 expression was also significantly associated with advanced T stage (p = 0.0069), N stage (p = 0.0088), and positive distant metastasis (p = 0.0076). Experimentally, elevated YTHDF3 expression was observed in STAD tissues and cells (all p < 0.001). Silencing YTHDF3 suppresses AGS malignancy and promotes apoptosis. Conversely, YTHDF3 overexpression aggravated the malignant phenotype of STAD (all p < 0.001). Mechanistically, silencing YTHDF3 promoted APC expression (p < 0.001) in an m⁶A-dependent manner. Rescue experiments proved silencing APC reversed YTHDF3-knockdown-mediated repression of Wnt/β-catenin signaling and AGS cell malignancy (all p < 0.001).

Conclusion: YTHDF3 promoted STAD progression by regulating APC mRNA degradation.

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YTHDF3通过促进m6a依赖性APC mRNA降解促进胃癌进展。

背景：胃腺癌（STAD）是一种非常普遍的恶性肿瘤。YTH结构域家族蛋白3 （YTHDF3）是一种m6A解读器，与STAD患者较差的生存结果相关。目的是研究YTHDF3对STAD细胞的影响及其潜在的调控机制。方法：采用流行病学方法，使用GEPIA和Kaplan-Meier Plotter数据库检测YTHDF3在STAD中的表达，并评估其与预后的关系，以总生存期（OS）定义不良预后。分析临床参数，验证YTHDF3的预后价值。实验选择STAD患者作为研究对象。免疫荧光法证实YTHDF3在STAD组织中的表达。体外实验检测了YTHDF3/大肠腺瘤性息肉病（APC）对Wnt信号的调控。结果：流行病学上，STAD患者YTHDF3升高（p < 0.05）预示较差的OS（风险比[HR] = 1.46, 95%可信区间[95% CI]: 1.17-1.81, p = 0.00066）。YTHDF3高表达也与晚期T期（p = 0.0069）、N期（p = 0.0088）和远处转移阳性（p = 0.0076）相关。实验中，YTHDF3在STAD组织和细胞中表达升高（均p < 0.001）。沉默YTHDF3可抑制AGS恶性肿瘤并促进细胞凋亡。相反，YTHDF3过表达加重了STAD的恶性表型（均p < 0.001）。在机制上，沉默YTHDF3以依赖m6a的方式促进APC表达（p < 0.001）。救援实验证明，沉默APC逆转了ythdf3敲低介导的Wnt/β-catenin信号传导抑制和AGS细胞恶性（均p < 0.001）。结论：YTHDF3通过调控APC mRNA降解促进STAD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。

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来源期刊

Analytical Cellular Pathology ONCOLOGY-CELL BIOLOGY

CiteScore

4.90

自引率

3.10%

发文量

审稿时长

16 weeks

期刊介绍： Analytical Cellular Pathology is a peer-reviewed, Open Access journal that provides a forum for scientists, medical practitioners and pathologists working in the area of cellular pathology. The journal publishes original research articles, review articles, and clinical studies related to cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, immunopathology, and hematology.