[Effect of on the Drug Resistance of Diffuse Large B-Cell Lymphoma Cells by Regulating PD-1/PD-L1 Signaling Pathway].

OBJECTIVE

To explore the effect of microRNA-424-5p (miR-424-5p) on the drug resistance of diffuse large B-cell lymphoma (DLBCL) cells by regulating the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling pathway.

METHODS

Human DLBCL cell line CRL2631 cells were induced to construct CRL2631-CHOP resistant cell line. RT-qPCR and Western blot were used to detect the expression levels of , PD-L1 mRNA and protein, and multidrug resistance gene-1 (MDR-1) protein in CRL2631 cells and CRL2631-CHOP cells, respectively. The target genes of was verified by dual luciferase reporter assay. The miRNA simulation/interference technology and thiazole blue (MTT) method were used to detect the resistance of CRL2631 cells and CRL2631-CHOP cells to CHOP.

RESULTS

Compared with CRL2631 cells, the drug resistance of CRL2631-CHOP cells to CHOP and the levels of MDR-1 protein (<0.05), PD-L1 mRNA and protein in the cells were significantly increased (both <0.001), while the relative level of was significantly reduced (<0.001). The result of the dual luciferase reporter assay showed that PD-L1 was the direct downstream target gene of (<0.001). After transfection of inhibitor, the resistance of CRL2631 cells to CHOP drugs increased, and the expression level of MDR-1 protein (<0.01), PD-L1 mRNA and protein also increased significantly (both <0.01). After transfection of mimics, the resistance of CRL2631-CHOP cells to CHOP drugs decreased, and the expression level of MDR-1 protein (<0.001), PD-L1 mRNA and protein also decreased significantly (both <0.001). Overexpression of PD-L1 could reverse the inhibitory effect of upregulating on PD-L1 (<0.001).

CONCLUSION

Down-regulation of enhances the drug resistance of DLBCL cells by regulating the PD-1/PD-L1 signaling pathway.