USP20 regulates the stability of EMT transcription factor SOX4 and influences colorectal cancer metastasis.

BACKGROUND: Colorectal cancer (CRC) is a familiar malignancy accompanied by higher morbidity and mortality. The deubiquitination enzyme USP20 has been discovered to be one key factor in several cancers progression. SOX4 is a critical transcription factor to regulate the expression of various genes, and participates into the occurrence and progression of cancers. In this study, it was aimed to illustrate the role of USP20 and the regulatory relationship between USP20 and SOX4 in CRC. METHODS: The protein expressions of USP20, SOX4, E-cadherin, N-cadherin, Snail and slug were tested through western blot. The cell proliferation ability was verified through CCK-8 assay. The migration and invasion abilities were detected through Transwell assay. The mRNA expression of SOX4 was confirmed through RT-qPCR. The interaction between USP20 and SOX4 was notarized through Co-IP assay. RESULT: Our study demonstrated that USP20 displayed higher expression, and facilitated CRC progression through regulating cell proliferation, migration, invasion and EMT process markers. USP20 was found to modulate SOX4 protein expression. Next, it was verified that USP20 regulated SOX4 degradation through deubiquitination. Finally, through rescue assays, we revealed that USP20 mediated SOX4 expression to accelerate CRC progression. CONCLUSIONS: In this study, USP20 regulated the stability of EMT transcription factor SOX4 and aggravated colorectal cancer metastasis. This finding might highlight the function of USP20 in the treatment of CRC.

[Surgical complications after pancreatoduodenectomy: risk factors and treatments].

OBJECTIVE: To explore the impact factors and treatment of post pancreatoduodenectomy complications. METHODS: The clinical data of 412 cases between January 1995 and April 2010 underwent pancreatoduodenectomy were analyzed retrospectively. There were 232 male, 180 female. Univariate and multivariate logistic regression model were used to identify the risk factors related to occurrence of postoperative complications. RESULTS: The overall postoperative morbidity rate was 37.1% (153/412), and mortality rate was 4.6% (19/412). Total uncinate process resection, type of pancreatic-enteric anastomosis, duct diameter and pancreatic texture had effects on postoperative pancreatic fistula statistically. Total uncinate process resection, the amount of intra-operative blood loss ≥ 600 ml and pancreatic fistula were identified as significant risk factors for post pancreatoduodenectomy hemorrhage by means of univariate analysis. Delayed gastric empting occurrence in the patients with pylorus-preserving pancreaticoduodenectomy was higher than those with standard pancreaticoduodenectomy significantly. The multivariate Logistic regression analysis revealed that duct diameter and pancreatic texture were the independent risk factors of pancreatic fistula. Total uncinate process resection, the amount of intra-operative blood loss ≥ 600 ml and pancreatic fistula were independent risk factors of bleeding. There were no statistically significant differences between the radical group and the standard group when postoperative complication rates were analyzed (P < 0.05). CONCLUSIONS: Pancreaticojejunal anastomoses by means of duct-to-mucosa is fit for the patients with dilated pancreatic duct and end-to-end invaginated pancreaticojejunostomy is fit for the patients with undilated pancreatic duct. The prevention of postoperative bleeding depends on total uncinate process resection and meticulous hemostatic technique during operation. The pancreatic fistula is one of the most important factors which can result in postoperative bleeding. Pancreaticoduodenectomy combines with SMV/PV resection and extended lymphadenectomy do not significantly increase the morbidity rates.

[Clinical analysis of post pancreatoduodenectomy hemorrhage].

OBJECTIVE: To explore the factors of post pancreatoduodenectomy hemorrhage. METHODS: The clinical data of 263 cases between January 1998 and April 2008 underwent pancreatoduodenectomy were analyzed prospectively. RESULTS: The overall mortality rate was 4.94% (13/263). Postoperative bleeding occurred in 23 patients (8.75%), with 8 episodes ending fatally (34.8%). The tumor size, Child classification, caput total resection and pancreatic leakage were identified as significant risk factors for post pancreatoduodenectomy hemorrhage by means of univariate analysis. The multivariate Logistic regression analysis revealed that all of the five factors turned out to be the independent risk factors. CONCLUSIONS: The prevention of these bleeding complications depends in the first place on meticulous hemostatic technique. The pancreatic leakage is also one of the most important factors due to postoperative bleeding. The prophylactic use of somatostatin is not necessary.

[The role of human fibroblast growth factor receptor 1-IIIb isoform in proliferation of pancreatic ductal cells and its effects to mitogen-activated protein kinase].

OBJECTIVE: To study the role of IIIb isoform of human fibroblast growth factor receptor 1 (FGFR1-IIIb) in proliferation of pancreatic ductal cells and its effects on mitogen-activated protein kinase (MAPK). METHODS: Human pancreatic ductal cells of the line TAKA-1 were cultured. The plasmid of human full-length FGFR1-IIIb isoform, pSVK4/FGFR1-IIIb, was stable transfected into the cultured TAKA-1 pancreatic ductal cells facilitated by lipofectamine. Un-transfected TAKA-1 cells and TAKA-1 ductal cells transfected with blank plasmid were used as controls. The expression, distribution and character of protein of FGFR1-IIIb in the TAKA-1 cells were estimated by Western blotting, Northern blotting, immunofluorescence assay, and glycosylation assay. The function and mechanism of FGFR1-IIIb in the transfected pancreatic ductal cells stimulated by FGF were examined by MTT assay and MAPK assay. Tunicamycin, an inhibitor of N-terminal glycoprotein synthesis, was added into the culture fluid of the FGFR1-IIIb transfected TAKA-1 cells to observe the changes of the FGFR1 bands. RESULTS: FGFR1-IIIb, a glycosylated receptor at various levels at 120 kDa and between 130 - 150 kDa, was localized at moderate levels at the cell membrane and cytoplasm and at higher level in the perinuclear region of the cytoplasm of the pSVK4/FGFR1-IIIb-transfected cells. FGF-1, -2, and -4 significantly increased the growth of FGFR1-IIIb-transfected TAKA-1 cells, and at the same time induced the p44/p42 MAPK phosphorylation. CONCLUSION: Human FGFR1-IIIb receptor is a functional receptor in pancreatic ductal cells. FGF-1, -2, and -4 can increase the growth of FGFR1-IIIb-transfected pancreatic ductal cells, and the mechanism is that they can induce the p44/p42 MAPK phosphorylation.