Background
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.
Conclusions
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.
Methods
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.
Results
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. Conclusions: 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.