VIM通过调控上皮-间质转化增强非小细胞肺癌顺铂耐药性OACHSSCD

Objective To screen potential key molecules regulating cisplatin resistance in non-small cell lung cancer(NSCLC)cells and validate their functions based on transcriptome sequencing analysis and cellular experiments.Methods Differentially expressed genes(DEGs)between human NSCLC A549 cells and their cisplatin-resistant A549/DDP cells were screened using transcriptome sequencing data from the GEO database.The enriched pathways of the DEGs were analyzed by KEGG and GO enrichment analyses.NSCLC cells were divided into a control group(A549 cells)and a drug-resistant group(A549/DDP cells).The expression of key DEGs in these two groups was detected by qRT-PCR and Western blotting.A vimentin(VIM)knockdown cell line(A549/DDP-siVIM)was constructed using transient interference technology,and the differences in drug resistance among this cell line(siVIM group),A549 cells(A549 group),and A549/DDP cells(DDP group)were analyzed.Results The cell scratch assay showed that compared with A549 cells,the in vitro migration ability ofA549/DDPcells was significantly enhanced(P<0.01).Transcriptome sequencing analysis identified 165 DEGs between A549 and A549/DDP cells.KEGG and GO enrichment analyses revealed that these DEGs were significantly enriched in pathways related to epithelial-mesenchymal transition(EMT),suggesting that EMT might be involved in regulating the enhanced migration ability of cisplatin-resistant cells.VIM was the most significantly differentially expressed gene between the two groups of cells.qRT-PCR and Western blotting confirmed that its expression level in A549/DDP cells was significantly higher than that in A549 cells.VIM interference in A549/DDP cells reduced the level of the mesenchymal marker N-cadherin,and analysis using the GEPIA database indicated that VIM expression was positively correlated with the expression of key EMT-inducing signaling molecules in NSCLC.The cell scratch assay demonstrated that VIM interference inhibited the migration ability of A549/DDP cells(P<0.01).The cell proliferation assay showed that under treatment with 8 mg/L cisplatin,the survival rate of A549/DDP cells was higher than that of A549 cells,whereas knocking down VIM significantly reduced their survival rate(P<0.01).Conclusion This study successfully identifies VIM as a key molecule regulating cisplatin resistance in NSCLC cells,which enhances the migration ability of drug-resistant cells and reduces their sensitivity to cisplatin,providing a new potential therapeutic target for reversing cisplatin resistance in NSCLC.