The Study On The Role And Mechanism Of Circ_MTHFD2 And MicroRNA-124 On Lung Cancer Resistance To Pemetrexed

Objective:To investigate the effect of microRNA-124?miR-124?mediated by circ_MTHFD2 on the resistance of lung cancer against pemetrexed.Methods:Bioinformatic analysis was used to detect the expression of miR-124 in A549cells and A549/PEM cells.Liposome transfection method was used to up-regulate and inhibit the expression of miR-124 in A549 cells,then the sensitivity to pemetrexed was estimated by CCK-8 assay and flow cytometry.Sequencing and bioinformatic analysis were used to detect the expression of circular RNA in different cells and tissue and to predict the binding sites between mi R-124 and circular RNA.Clinical specimens were used to identify the relationship between the expression of circ_MTHFD2 and the recurrence-free survival time?RFS?in patients with lung cancer.Results:In A549/PEM cells,the expression of miR-124 was significantly decreased.Compared with control group,the sensitivity to pemetrexed is significantly reduced in A549/miR-124 inhibitor group,and the IC₅₀0 was?9.94±1.90?and?80.45±3.50??mol/L respectively,with a significant difference between two groups?P<0.05?.Transfection of A549,A549/PEM cells with mimics of miR-124 showed that apoptosis is more significant than control group.The sequencing indicated that the expression of many circular RNAs are up-regulated in resistant cells and one of them,circ_MTHFD2,was proposed to bind miR-124.By the detection of clinical specimens,we found that circ_MTHFD2 is negatively correlated with RFS,the correlative coefficient is 0.71367.Conclusion:circ_MTHFD2/miR-124 regulation contributes to the development of pemetrexed resistance in lung carcinoma,which may be related to the survival and prognosis of lung cancer patients.