Zhou Ming, Mao Xiaozhe, Shen Kanger, Zhan Qin, Ni Haoxiang, Liu Chun, Huang Ziyi, Li Rui
Jiangsu Institute of Clinical Immunology, First Affiliated Hospital of Soochow University, Suzhou, China; Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, China.
Jiangsu Institute of Clinical Immunology, First Affiliated Hospital of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, China.
Pathol Res Pract. 2025 May;269:155899. doi: 10.1016/j.prp.2025.155899. Epub 2025 Mar 23.
Gastric cancer (GC) ranks among the most common gastrointestinal tumours and is a significant contributor to cancer mortality globally. The proliferation, metastasis, occurrence and development of GC have obvious malignant tendencies. This study is based on our previous studies. Previously, we reported that Fibulin-2 (FBLN2) can inhibit the distant metastasis of GC by promoting lost-nest apoptosis. Despite its clinical importance, the biological function of FBLN2 in GC remains inadequately understood. This study investigated the underlying molecular mechanisms of FBLN2 in the pathogenesis and progression of GC, as well as its impact on the biological behaviour of GC cells. In vivo and in vitro experiments, we demonstrated that FBLN2 overexpression resulted in a reduction in GC cell proliferation and metastasis, whereas its knockdown led to enhancement of GC proliferation and metastasis. Moreover, we used RNA-seq technology to conduct KEGG enrichment analysis of differential genes in wild-type GC cells and FBLN2 knockout GC cells and successfully confirmed that FBLN2 plays a corresponding biological role through the TGFβ/TGIF2 axis. In addition, in terms of the clinical data, we revealed a correlation between FBLN2 and TGIF2 and patient prognosis. In summary, our study revealed that FBLN2 suppressed GC proliferation, migration and invasion by downregulating the TGFβ/TGIF2 axis, suggesting that FBLN2 is a promising target for GC treatment.
胃癌（GC）是最常见的胃肠道肿瘤之一，也是全球癌症死亡率的重要贡献因素。GC的增殖、转移、发生和发展具有明显的恶性倾向。本研究基于我们之前的研究。此前，我们报道纤连蛋白-2（FBLN2）可通过促进失巢凋亡来抑制GC的远处转移。尽管FBLN2具有临床重要性，但其在GC中的生物学功能仍未得到充分了解。本研究探讨了FBLN2在GC发病机制和进展中的潜在分子机制，以及其对GC细胞生物学行为的影响。在体内和体外实验中，我们证明FBLN2过表达导致GC细胞增殖和转移减少，而其敲低则导致GC增殖和转移增强。此外，我们使用RNA测序技术对野生型GC细胞和FBLN2基因敲除GC细胞中的差异基因进行KEGG富集分析，并成功证实FBLN2通过TGFβ/TGIF2轴发挥相应的生物学作用。此外，就临床数据而言，我们揭示了FBLN2与TGIF2及患者预后之间的相关性。总之，我们的研究表明FBLN2通过下调TGFβ/TGIF2轴抑制GC的增殖、迁移和侵袭，提示FBLN2是GC治疗的一个有前景的靶点。
