Перегляд вихідного коду сторінки Science Technician Discovers Harmful Transducin Compulsion

, 2000). The IG10 cells stably expressing luciferase were generated for monitoring tumor growth in?vivo. Control and DDX1-silenced IG10 cells (1?�� 106) were injected into the peritoneal cavity of C57BL/6N mice (n?= 10 per group). Tumor growth within the peritoneal cavity and buildup ascites were monitored. We observed dramatic increases of luminescence in the mice bearing tumors derived from the DDX1-silenced cells (Figure?6B). After 8?weeks, the animals were sacrificed and inspected for tumor weights and tumor nodules. Depletion of DDX1 resulted in profound increases in tumor weight (161.6% increase; p?[http://en.wikipedia.org/wiki/Transducin Transducin] to common metastatic sites (mesentery, omentum, diaphragm, perihepatic sites, pelvic and paraaortic lymph nodes, and kidney) of high-grade serous ovarian carcinoma (Figures 6D and 6E). In the DDX1-silenced tumors, the levels of miR-200a/miR-200b were significantly decreased, whereas their targets ZEB1 and ZEB2 were induced (Figure?6F). To assess whether knockdown of DDX1 promotes EMT in?vivo, we measured the [http://www.selleckchem.com/products/otx015.html www.selleckchem.com/products/otx015.html] levels of ZEB1, E-cadherin, and Vimentin in control and DDX1-silenced tumors. In comparison with the control, the DDX1-silenced tumors exhibited elevated levels of ZEB1 (145% increase; p?= 0.017) and Vimentin (150% increase; p?= 0.011) and decreased levels of E-cadherin (61% reduction; p?= 0.009) (Figure?6G). Taken together, [http://www.selleckchem.com/btk.html http://www.selleckchem.com/btk.html] these results suggest that suppression of DDX1 promotes ovarian tumor progression. To determine the correlation between DDX1 levels and clinical outcome of patients with cancer, we analyzed the expression of DDX1 and miRNAs and the correlation between DDX1 and overall patient survival in The Cancer Genome Atlas (TCGA). We randomly split the entire population of patients with certain types of cancer into training/validation cohorts. Analysis of both cohorts across cancer types revealed that low levels of DDX1 are significantly associated with poor overall survival in patients with serous ovarian adenocarcinoma and in patients with kidney renal clear cell carcinoma (Figures 7A, 7B, S7A, and S7B). In the validation cohort of ovarian adenocarcinomas, the median survival of patients with high-DDX1 ovarian cancer is 70.8?months, which is remarkably better than 38.4?months for patients with low-DDX1 ovarian cancer (p?= 0.01075) (Figure?7A). Levels of miR-200a and miR-200c in DDX1-high ovarian tumors are 2.1-fold (p?= 0.006) and 1.8-fold (p?= 0.04) higher than those in DDX1-low tumors, respectively, in the validation data set (Figure?7C). The positive correlation between DDX1 and miR-200 levels was also observed in the training set (Figure?S7C).