The effect of NPM1 silencing on the tumorigenesis of drug-resistant bladder cancer and related signaling pathway

Abstract

Background: NPM1 can provide abundant information of bladder cancer changes, but the effect of NPM1 differential expression on tumor and tumor related molecular mechanism has not been elucidated.Methods: NPM1 silencing cell line was established by lentivirus. The tumorigenic ability was judged by wound-healing assay, transwell invasion assay and nude mice tumorigenicity assay. The proteome of NPM1 deficient bladder cancer cell line was analyzed by Liquid Chromatography Mass Spectrometry (LC-MS). The results of mass spectrometry are comprehensively analyzed by bioinformatics analysis for tumor related molecules. The signal pathways involved in tumor related molecules will be verified by KEGG and UniProt databases.Results: Compared with the corresponding negative control group, NPM1 silencing cell line T24/DDP Lv-NPM1 showed strong migration ability and high invasive ability. There was no significant difference in migration ability and the invasive cells proportion between NPM1 overexpressing cell line and related negative control group. The tumorigenesis in nude mice also showed that NPM1 silencing tumor had larger tumor volume. Among all differential proteins analyzed by mass spectrometry, 20 proteins with signal transduction activity showed the most significant difference (Fold change > 1.5). 6 of them were associated with NF-κB signaling pathway, which may play an important role in the development of tumor.Conclusions: The loss of NPM1 may indicate the poor outcome of bladder cancer. Abnormal expression of NF-κB signaling pathway is an important factor in the progression of bladder cancer. Monitoring NPM1 expression can effectively adjust the treatment strategy of bladder cancer.