Influenza is an acute respiratory infection caused by the influenza virus, and vaccination against influenza is considered the best way to prevent the onset and spread. MDCK (Madin-Darby canine kidney) cells are typically used to isolate the influenza virus, however, their high tumorigenicity is the main controversy in the production of influenza vaccines. Here, MDCK-C09 and MDCK-C35 monoclonal cell lines were established, which were proven to be low in tumorigenicity. RNA-seq of MDCK-C09, MDCK-C35, and MDCK-W73 cells was performed to investigate the putative tumorigenicity mechanisms. Tumor-related molecular interaction analysis of the differentially expressed genes indicates that hub genes, such as CUL3 and EGFR, may play essential roles in tumorigenicity differences between MDCK-C (MDCK-C09 and MDCK-C35) and MDCK-W (MDCK-W73) cells. Moreover, the analysis of cell proliferation regulation-associated molecular interaction shows that downregulated JUN and MYC, for instance, mediate increased proliferation of these cells. The present study provides a new low-tumorigenic MDCK cell line and describes the potential molecular mechanism for the low tumorigenicity and high proliferation rate.

流感是由流感病毒引起的急性呼吸道感染，接种流感疫苗被认为是预防其发生和传播的最佳方式。MDCK（Madin-Darby 犬肾）细胞通常用于分离流感病毒，然而，它们的高致瘤性是流感疫苗生产中的主要争议。在这里，建立了 MDCK-C09 和 MDCK-C35 单克隆细胞系，它们被证明是低致瘤性的。对 MDCK-C09、MDCK-C35 和 MDCK-W73 细胞进行 RNA-seq 以研究推定的致瘤机制。差异表达基因的肿瘤相关分子相互作用分析表明，枢纽基因，如CUL3和EGFR，可能在 MDCK-C（MDCK-C09 和 MDCK-C35）和 MDCK-W（MDCK-W73）细胞之间的致瘤性差异中起重要作用。此外，细胞增殖调控相关分子相互作用的分析表明，例如，下调的JUN和MYC介导了这些细胞的增殖增加。本研究提供了一种新的低致瘤性 MDCK 细胞系，并描述了低致瘤性和高增殖率的潜在分子机制。