Bridging intergrator-1 inhibits the expression of PD-L1 through c-MYC pathway in non-small cell lung cancerA549 cells / 中国肿瘤生物治疗杂志

ABSTRACT

@# Objective: To investigate the effect and mechanism of bridging intergrator-1 (BIN1) on expression of programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) A549 cells. Methods: Quantitative real-time polymerase chain reaction (qRTPCR) and Western blotting were used to detect the mRNA and protein expression of BIN1 and PD-L1 in A549 cells and normal human embryo lung fibroblast 2BS cells, respectively. Eukaryotic expression plasmid CMV-MCS-GFP-SV40-Neomycin-BIN1 containing human full length BIN1 gene sequence was transfected into A549 cells via cationic liposomes by using gene transfection technology (as BIN1+group); c-MYC-siRNAwas used to knockdown the expression of c-MYC inA549 cells through RNAinterference technique (as cMYC-siRNA group). The transfection efficiencies were verified by qRT-PCR and Western blotting, the effects of BIN1 over-expression and c-MYC knock-down on the expression of c-MYC and PD-L1 in A549 cells were detected as well. Results: Comparing with 2BS cells, the expression of BIN1 was down-regulated in A549 cells at both mRNA and protein levels, while the expression of PD-L1 was up-regulated (all P<0.05). The expression of BIN1 was increased at both mRNA and protein level in BIN1+ group, while the expression of PD-L1 was decreased significantly after B1N1 transfection (all P<0.05). After transfection of c-MYC-siRNA into A549 cells, the expression of c-MYC and PD-L1 in c-MYC-siRNAgroup was down-regulated significantly (all P<0.01). Conclusion: Over-expression of BIN1 could reduce the expression of PD-L1 by inactivating the c-MYC pathway, thereby inhibiting the immune escape ofA549 cells.