胃癌（GC）是全球癌症相关死亡的主要原因，因此需要确定新的治疗靶点。本研究通过上皮间质转化 (EMT) 途径探讨 MATN3 和 ASPN 在 GC 进展中的作用。对癌症基因组图谱-胃癌 (TCGA-STAD) 数据集的分析表明，MATN3 和 ASPN 在 GC 组织中均显着上调，并与患者生存率较差相关。蛋白质-蛋白质相互作用和共表达分析证实了 MATN3 和 ASPN 之间的直接相互作用，表明它们在 EMT 激活中具有协同作用。功能分析表明，MATN3 促进 GC 细胞增殖、迁移和侵袭，而其敲低则抑制这些恶性行为并诱导细胞凋亡。 ASPN 过度表达进一步放大了这些致癌作用。在体内，小鼠模型的研究证实，MATN3 和 ASPN 的共过表达可增强肿瘤生长和转移。这些发现强调了 MATN3-ASPN 轴作为 GC 的潜在治疗靶点，为驱动 GC 进展的分子机制提供了新的见解。© 作者 2024。由牛津大学出版社出版。版权所有。如需权限，请发送电子邮件至：journals.permissions@oup.com。

Gastric cancer (GC) is a leading cause of cancer-related deaths globally, necessitating the identification of novel therapeutic targets. This study investigates the roles of MATN3 and ASPN in GC progression via the epithelial-mesenchymal transition (EMT) pathway. Analysis of the Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD) dataset revealed that both MATN3 and ASPN are significantly upregulated in GC tissues and correlate with poor patient survival. Protein-protein interaction and co-expression analyses confirmed a direct interaction between MATN3 and ASPN, suggesting their synergistic role in EMT activation. Functional assays demonstrated that MATN3 promotes GC cell proliferation, migration, and invasion, while its knockdown inhibits these malignant behaviors and induces apoptosis. ASPN overexpression further amplified these oncogenic effects. In vivo, studies in a mouse model corroborated that co-overexpression of MATN3 and ASPN enhances tumor growth and metastasis. These findings highlight the MATN3-ASPN axis as a potential therapeutic target in GC, offering new insights into the molecular mechanisms driving GC progression.© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.