背景：目前胃癌（GC）特别是晚期GC的临床治疗缺乏可靠的治疗靶点。 3'-非翻译区（3'-UTR）作为药物靶点引起了越来越多的关注。方法：通过体外和体内实验确定FN1 3'-UTR和FN1蛋白在侵袭和转移中的功能。采用RNA Pull-down实验和高通量测序筛选FN1 3'-UTR调控因子并构建调控网络。使用蛋白质印迹和聚合酶链反应来检查分子间表达水平的相关性。 RNA结合蛋白免疫沉淀用于验证FN1 3'-UTR与靶mRNA之间的相关性。结果：在 GC 患者中，FN1 3'-UTR 可能比 FN1 蛋白具有更强的预后意义。在体外和体内，FN1 3'-UTR 的上调比 FN1 蛋白更能显着促进 GC 细胞的侵袭和转移能力。基于FN1 3'-UTR-let-7i-5p-THBS1轴构建了一个新的调控网络，其中FN1 3'-UTR表现出比FN1蛋白更强的致癌作用。结论：FN1 3'-UTR 可能是比 FN1 蛋白更好的构建 GC 靶向药物的治疗靶点。© 作者。

Background: Current clinical treatments for gastric cancer (GC), particularly advanced GC, lack infallible therapeutic targets. The 3'-untranslated region (3'-UTR) has attracted increasing attention as a drug target. Methods: In vitro and in vivo experiments were conducted to determine the function of FN1 3'-UTR and FN1 protein in invasion and metastasis. RNA pull-down assay and high-throughput sequencing were used to screen the factors regulated by FN1 3'-UTR and construct the regulatory network. Western blotting and polymerase chain reaction were used to examine the correlation of intermolecular expression levels. RNA-binding protein immunoprecipitation was used to verify the correlation between FN1 3'-UTR and target mRNAs. Results: The FN1 3'-UTR may have stronger prognostic implications than the FN1 protein in GC patients. Upregulation of FN1 3'-UTR significantly promoted the invasive and metastatic abilities of GC cells to a greater extent than FN1 protein in vitro and in vivo. A novel regulatory network was constructed based on the FN1 3'-UTR-let-7i-5p-THBS1 axis, wherein FN1 3'-UTR displayed stronger oncogenic effects than the FN1 protein. Conclusions: FN1 3'-UTR may be a better therapeutic target for constructing targeted drugs in GC than the FN1 protein.© The author(s).