Cancer Management and Research (Nov 2020)
miR-124-3p Regulates FGF2–EGFR Pathway to Overcome Pemetrexed Resistance in Lung Adenocarcinoma Cells by Targeting MGAT5
Abstract
Jundong Cai,1 Jiuning Huang,1,2 Wulong Wang,1 Jing Zeng,1 Ping Wang1 1Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300000, People’s Republic of China; 2Department of Radiotherapy, Yantai Affiliated Hospital of Binzhou Medical University, Yantai 264000, Shandong, People’s Republic of ChinaCorrespondence: Ping WangDepartment of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin 300000, People’s Republic of ChinaTel +86-18622221112Email [email protected]: To 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.Methods: PC9-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.Results: The 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).Conclusion: miR-124-3p may inhibit the FGF2–EGFR pathway by targeting MGAT5 to decrease pemetrexed resistance in lung adenocarcinoma cells.Keywords: miR-124-3p, MGAT5, FGF2-EGFR pathway, lung adenocarcinoma
