MiR-124-3p Regulates FGF2-EGFR Pathway to Overcome Pemetrexed Resistance in Lung Adenocarcinoma Cells by Targeting MGAT5.

Abstract

ObjectiveTo investigate whether miR-124-3p regulates the fibroblast growth factor 2 (FGF2)–epidermal growth factor receptor (EGFR) pathway by targeting MGAT5 to affect the pemetrexed resistance in lung adenocarcinoma cells.MethodsPC9-MTA and H1993-MTA anti-pemetrexed lung adenocarcinoma cell lines were constructed. The cell viability of anti-pemetrexed and parent lung adenocarcinoma cells was analyzed using MTS assay and reverse transcription PCR to determine the expression of miR-124-3p. CCK8 assay, colony formation assay, and flow cytometry were used to determine cells’ proliferation and apoptosis. FGF2–EGFR signaling pathway-related proteins and MGAT5 protein expression were quantified by Western blotting. The target relationship between miR-124-3p and MGAT5 was verified by double luciferase assay. A nude mouse model with a transplanted tumor was established using the anti-pemetrexed lung adenocarcinoma cells. Tumor volume and weight were determined, and the apoptosis of tumor cells was observed.ResultsThe half-maximal inhibitory concentration of pemetrexed in anti-pemetrexed lung adenocarcinoma cells was higher than that in parent lung adenocarcinoma cells, and the expression of miR-124-3p in the anti-pemetrexed cells was lower than that of the parent cells. In the miR-124-3p overexpression group, MGAT5 silencing group, and miR-124-3p+MGAT5 overexpression group, compared with the control group, the proliferation ability of cells and tumors was markedly reduced; their apoptosis rates were increased significantly; expression levels of FGF2 and p-EGFR/EGFR were decreased; and the growth rate and tumor volume and mass were reduced; however, the opposite results were obtained in the miR-124-3p silencing group (p<0.05).ConclusionmiR-124-3p may inhibit the FGF2–EGFR pathway by targeting MGAT5 to decrease pemetrexed resistance in lung adenocarcinoma cells.