Abstract
Fibroblast growth factor receptor 1 (FGFR1) has been reported in gastric cancer to be a prognostic factor. However, miR-497-targeted FGFR1 has not been explored in the carcinogenesis of gastric cancer. The present study intended to revalidate the prognostic significance of FGFR1 in patients with gastric cancer, and the mechanism of miR-497-regulated FGFR1 was investigated in gastric cancer cell proliferation and apoptosis. The messenger RNA (mRNA) and protein levels were assayed by RT-qPCR and western blotting, respectively. The targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Cell proliferation was analyzed by CCK-8 assay. Annexin V-FITC/PI staining was used to evaluate the apoptosis in AGS and SGC-7901 cells. FGFR1 was frequently up-regulated in gastric cancer tissues and associated with poor overall survival in patients with gastric cancer. Interestingly, FGFR1 loss-of-function resulted in a significant growth inhibition and apoptosis in AGS and SGC-7901 cells. In addition, we found that miR-497 was inhibited in gastric cancer tissues and cell lines, while overexpression of miR-497 could suppress proliferation and induce apoptosis in AGS and SGC-7901 cells. Importantly, bioinformatics analysis and experimental data suggested that FGFR1 was a direct target of miR-497, which could inhibit FGFR1 expression when transfected with miR-497 mimics. Furthermore, we found that overexpression of FGFR1 reversed the growth inhibition and apoptosis of miR-497 mimics in AGS and SGC-7901 cells. These findings suggested that overexpression of miR-497 inhibited proliferation and induced apoptosis in gastric cancer through the suppression of FGFR1.
Highlights
The fibroblast growth factor receptor (FGFR) family is composed of four members, Fibroblast growth factor receptor 1 (FGFR1)/2/3/4, which are activated by interacting with fibroblast growth factors (FGFs), resulting in the activation of downstream signaling pathways including mitogen-activated protein kinase signal transducer and activator of transcription and PI3K/ Akt/mTOR signaling [1,2]
The findings showed that patients with high messenger RNA (mRNA) expression of FGFR1 resulted in a significantly poorer prognosis compared with patients with a low level of FGFR1 (Figure 1E)
FGFR1 was up-regulated in gastric cancer tissues and cell lines and associated with poor survival prognosis, metastasis, and TNM stage, suggesting that FGFR1 played a crucial role in the carcinogenesis of gastric cancer
Summary
The fibroblast growth factor receptor (FGFR) family is composed of four members, FGFR1/2/3/4, which are activated by interacting with fibroblast growth factors (FGFs), resulting in the activation of downstream signaling pathways including mitogen-activated protein kinase signal transducer and activator of transcription and PI3K/ Akt/mTOR signaling [1,2]. FGFR1 belongs to receptor tyrosine kinases and possesses various biological functions, such as proliferation, survival, migration, and differentiation [3]. FGFR1 is expressed on a number of different cell types including tumor cells [4,5]. A meta-analysis and clinical survey suggest that FGFR1 is emerging as a diagnostic and prognostic marker for non-small-cell lung cancer (NSCLC) [9,10]. Its functional contributions have not been completely clarified in gastric cancer
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