Wilms tumor gene (WT1) is a marker for diagnosis and prognosis of ovarian cancer, but its molecular mechanism in ovarian cancer needs further study. Here, the results showed that WT1 was highly expressed in ovarian cancer and was closely associated with overall survival and progression-free survival (PFS) of ovarian cancer. In the ovarian cancer cell line SKOV3, WT1 downregulation led to increased mRNA expression of 638 genes and decreased mRNA expression of 512 genes, which were enriched in FoxO, AMPK, and Hippo signaling pathways. Protein-protein interaction (PPI) network was constructed using the STRING online tool and Cytoscape software and module analysis was performed to screen out 18 differentially expressed genes (DEGs). Kaplan-Meier plot analysis showed that 16 of the 18 genes were associated with prognosis. GEPIA dataset analysis showed that 7 of the 16 genes were differentially expressed in ovarian cancer tissues and normal tissues. After WT1 interference, IGFBP1 and FBN1 gene expression was significantly upregulated, while SERPINA1 gene expression was significantly downregulated. The expression of WT1 was consistent with the correlation of these three genes in ovarian cancer tissues and normal tissues. GeneMANIA online website analysis showed that there were complex interactions between WT1, IGFBP1, FBN1, SERPINA1 and 20 other genes. These research results provide a basis for clarifying the expression mechanism of the WT1 gene in ovarian cancer and provide a theoretical basis for new treatments for ovarian cancer.
CCK and transwell experiments verified the effect of WT1 downregulation on the proliferation, migration and invasion of the ovarian cancer cell line SKOV3. As shown in Figure 1A, WT1 downregulation had no significant effect on the proliferation of SKOV3. WT1 downregulation significantly increased the migration ability of cells (Figure 1B), and the invasion ability of cells was also significantly improved (Figure 1C). Transwell experiments further verified the effect of WT1 upregulation on the ovarian cancer cell line SKOV3. After 24 hours of infection with WT1-expressing adenoviruses, the WT1 infection rate of cells was >80%, and the WT1 protein was mainly localized in the nucleus (Figure 1D). As shown in Figure 1E, WT1 upregulation significantly inhibited the migration ability of cells.
Figure 1. The effect of WT1 on the proliferation, migration and invasion of ovarian cancer cell line SKOV3. (Meng K, et al., 2021)
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The WT1 adenovirus has been instrumental in our oncogene research. The virus demonstrates high infectivity and reproducible results. I will definitely order again!
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