Effect of MiR-424-5p on the Drug Resistance of Diffuse Large B-Cell Lymphoma Cells by Regulating PD-1/PD-L1 Signaling Pathway.
10.19746/j.cnki.issn.1009-2137.2023.01.015
- Author:
Jun YUAN
1
;
Hu HAN
2
;
Wei DONG
3
;
Rui-Cang WANG
1
;
Hong-Ling HAO
4
Author Information
1. Department of Hematology, Hebei General Hospital, Shijiazhuang 050055, Hebei Province, China.
2. Emergency Department, Hebei General Hospital, Shijiazhuang 050055, Hebei Province, China.
3. Department of Cardiology, The Third Hospital of Shijiazhuang, Shijiazhuang 050000, Hebei Province, China.
4. Department of Hematology, Hebei General Hospital, Shijiazhuang 050055, Hebei Province, China.E-mail: qdl382@163.com.
- Publication Type:Journal Article
- Keywords:
diffuse large B-cell lymphoma;
drug resistance;
microRNA-424-5p;
programmed death ligand-1;
programmed death receptor-1
- MeSH:
Humans;
B7-H1 Antigen/metabolism*;
Cell Line, Tumor;
Drug Resistance;
Luciferases;
Lymphoma, Large B-Cell, Diffuse/pathology*;
MicroRNAs/metabolism*;
Programmed Cell Death 1 Receptor;
RNA, Messenger;
Signal Transduction
- From:
Journal of Experimental Hematology
2023;31(1):96-103
- CountryChina
- Language:Chinese
-
Abstract:
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 MiR-424-5p, 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 MiR-424-5p 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 (P<0.05), PD-L1 mRNA and protein in the cells were significantly increased (both P<0.001), while the relative level of MiR-424-5p was significantly reduced (P<0.001). The result of the dual luciferase reporter assay showed that PD-L1 was the direct downstream target gene of MiR-424-5p (P<0.001). After transfection of MiR-424-5p inhibitor, the resistance of CRL2631 cells to CHOP drugs increased, and the expression level of MDR-1 protein (P<0.01), PD-L1 mRNA and protein also increased significantly (both P<0.01). After transfection of MiR-424-5p mimics, the resistance of CRL2631-CHOP cells to CHOP drugs decreased, and the expression level of MDR-1 protein (P<0.001), PD-L1 mRNA and protein also decreased significantly (both P<0.001). Overexpression of PD-L1 could reverse the inhibitory effect of upregulating MiR-424-5p on PD-L1 (P<0.001).
CONCLUSION:Down-regulation of MiR-424-5p enhances the drug resistance of DLBCL cells by regulating the PD-1/PD-L1 signaling pathway.
