Accumulating evidence highlights the critical roles of fibroblast growth factors (FGFs) in regulating the progression of multiple human cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the role of FGF11 in the progression of NSCLC. Previously published transcriptomic data (GSE75037 and GSE81089) were used to compare FGF11 expression level between NSCLC tumor tissues and adjacent normal tissues. 100 cases of NSCLC tumor tissues and 30 cases of matched adjacent normal tissues were used to validate FGF11 expression at mRNA and protein level by qPCR and immunohistochemistry. Bioinformatics analysis and dual luciferase reporter analysis were performed to confirm the regulatory effect of miR-525-5p on FGF11 expression. CCK-8 assay and transwell migration assay were employed to examine cellular proliferation, migration and invasion. Gene set enrichment analysis (GSEA) was performed to identify the signaling pathway associated with FGF11 expression. Finally, the functional role of FGF11 in NSCLC tumor growth was evaluated by in vivo study. FGF11 was upregulated in NSCLC tumor tissues and tumor cell lines. High FGF11 expression was associated with a poor prognosis in NSCLC patients. In vitro loss- and gain-of function experiments demonstrated that FGF11 knockdown inhibited, whereas FGF11 overexpression promoted the proliferation, migration and invasion of NSCLC cells. Dual luciferase reporter assay confirmed that FGF11 was downregulated by miR-525-5p, and the effect of FGF11 on cell proliferation, migration and invasion could be interfered by miR-525-5p. GSEA analysis further revealed that FGF11 expression was enriched with genes in hypoxia signaling pathway and the oncogenic function of FGF11 could be suppressed by knocking down HIF-1α in NSCLC cells. Moreover, FGF11 knockdown suppressed NSCLC tumor growth whereas FGF11 overexpression promoted tumor growth in vivo. Our study showed that FGF11 functions as an oncogene in tumor NSCLC progression. miR-525-5p seems to negatively regulate FGF11 and the oncogenic role of FGF11 is dependent on the upregulation of HIF-1α. Our study suggests that targeting FGF11 and HIF-1α may serve as novel strategies for the treatment of NSCLC.

中文翻译：

---

成纤维细胞生长因子 11 (FGF11) 通过调节缺氧信号通路促进非小细胞肺癌 (NSCLC) 进展

越来越多的证据强调了成纤维细胞生长因子 (FGFs) 在调节多种人类癌症（包括非小细胞肺癌 (NSCLC)）进展中的关键作用。在本研究中，我们研究了 FGF11 在 NSCLC 进展中的作用。先前发表的转录组数据（GSE75037 和 GSE81089）用于比较 NSCLC 肿瘤组织和相邻正常组织之间的 FGF11 表达水平。使用 100 例 NSCLC 肿瘤组织和 30 例匹配的相邻正常组织，通过 qPCR 和免疫组织化学验证 FGF11 在 mRNA 和蛋白水平的表达。进行生物信息学分析和双荧光素酶报告基因分析以确认 miR-525-5p 对 FGF11 表达的调节作用。CCK-8 测定和 transwell 迁移测定用于检查细胞增殖，迁移和入侵。进行基因集富集分析 (GSEA) 以确定与 FGF11 表达相关的信号通路。最后，通过体内研究评估了 FGF11 在 NSCLC 肿瘤生长中的功能作用。FGF11 在 NSCLC 肿瘤组织和肿瘤细胞系中上调。高 FGF11 表达与 NSCLC 患者的不良预后相关。体外功能丧失和获得实验表明，FGF11 敲低抑制，而 FGF11 过表达促进 NSCLC 细胞的增殖、迁移和侵袭。双荧光素酶报告基因检测证实FGF11被miR-525-5p下调，FGF11对细胞增殖、迁移和侵袭的影响可被miR-525-5p干扰。GSEA分析进一步表明，FGF11表达富含缺氧信号通路中的基因，并且可以通过敲低NSCLC细胞中的HIF-1α来抑制FGF11的致癌功能。此外，FGF11 敲低抑制 NSCLC 肿瘤生长，而 FGF11 过表达促进体内肿瘤生长。我们的研究表明，FGF11 在肿瘤 NSCLC 进展中作为癌基因发挥作用。miR-525-5p 似乎负调节 FGF11，FGF11 的致癌作用取决于 HIF-1α 的上调。我们的研究表明，靶向 FGF11 和 HIF-1α 可作为治疗 NSCLC 的新策略。我们的研究表明，FGF11 在肿瘤 NSCLC 进展中作为癌基因发挥作用。miR-525-5p 似乎负调节 FGF11，FGF11 的致癌作用取决于 HIF-1α 的上调。我们的研究表明，靶向 FGF11 和 HIF-1α 可作为治疗 NSCLC 的新策略。我们的研究表明，FGF11 在肿瘤 NSCLC 进展中作为癌基因发挥作用。miR-525-5p 似乎负调节 FGF11，FGF11 的致癌作用取决于 HIF-1α 的上调。我们的研究表明，靶向 FGF11 和 HIF-1α 可作为治疗 NSCLC 的新策略。