Background
The five-year survival rate of non-small cell lung cancer (NSCLC) patients is very low. MiR-873 is involved in the growth, metastasis, and differentiation of tumors. Herein, we determined the target gene and influence of miR-873 in NSCLC.
Conclusions
GLI1 is a target gene of miR-873 in NSCLC. The inhibition of miR-873 increased gefitinib resistance of NSCLC cells via the upregulation of GLI1. These results indicate that miR-873-GLI1 signaling is involved in gefitinib resistance in NSCLC.
Methods
MiRanda and Targetscan websites were used to predict the target gene of miR-873 in NSCLC. Luciferase activity was examined using a dual luciferase reporter gene assay kit. The viability, tube formation, and proliferation of cells were analyzed by cell counting kit-8, angiogenic analysis, and flow cytometry, respectively. The levels of miR-873 and GLI1 were evaluated using quantitative real-time PCR and Western blot assays.
Results
Low levels of GLI1 and high levels of miR-873 were observed in an NSCLC cell line (PC9) highly sensitive to EGFR-tyrosine kinase inhibitors. There was a negative correlation between miR-873 and GLI1 expression in PC9 and PC9/GR cells. The inhibition of miR-873 enhanced GLI1 levels. MiR-873 expression was inhibited by gefitinib. Gefitinib markedly reduced the viability, tube formation, and cell number in PC9 cells. However, suppression of miR-873 enhanced the resistance and knockdown of GLI1 enhanced the sensitivity of PC9 cells to gefitinib. Conclusions: GLI1 is a target gene of miR-873 in NSCLC. The inhibition of miR-873 increased gefitinib resistance of NSCLC cells via the upregulation of GLI1. These results indicate that miR-873-GLI1 signaling is involved in gefitinib resistance in NSCLC.