SUMO-specific protease 6 promotes gastric cancer cell growth via deSUMOylation of FoxM1.

SUMOylation is a post-translational modification exerted various effects on the target proteins. SUMOylation is a highly dynamic and reversible process, which has been shown to play an important role in tumorigenesis. However, the roles of sentrin/SUMO-specific proteases (SENPs), which mediate the reverse process of SUMOylation, in tumorigenesis remains largely unexplored. Here, we uncover a critical role of SENP6 in promoting gastric cancer cells growth via regulating the deSUMOylation of a transcription factor forkhead box protein M1 (FoxM1). We demonstrated that the mRNA and protein levels were elevated in gastric cancer tissues. Overexpression of SENP6 promoted, while RNA interference depletion of endogenous SENP6 inhibited gastric cancer cells growth and the ability of colony formation. By using biochemical assays, we identified FoxM1 as a novel substrate of SENP6 in gastric cancer cells. Thus, our data suggest that SENP6, which is highly expressed in gastric cancer cells, regulates the transcriptional activity and stability of FoxM1 through deSUMOylation.

[Clinical values of detecting excision repair cross complementing 1 and top-isomerase I in individualized therapies of metastatic colorectal cancer].

OBJECTIVE: To explore the clinical values of detecting drug related molecules excision repair cross complementing 1 (ERCC1) and top-isomerase I (TOPO I) in individualized therapies of metastatic colorectal cancer. METHODS: From June 2009 to December 2011, 90 patients at Huadong Hospital with metastatic colorectal cancer were randomly separated into 2 groups after operation. Each group had 45 patients without difference in gender, age or TNM stage. The expressions of ERCC1 and TOPO Iin cancer tissues were detected by immunohistochemical staining. The testing group received individualized chemotherapies following the expression results while the control group had random chemotherapies. The survival difference between two groups was analyzed by log-rank test and Kaplan-Meier analysis. And curative effect was analyzed by χ(2) or Fisher's analysis. RESULTS: The expressions of ERCC1 and TOPO I had no statistical significance between two groups (both P > 0.05). In the testing group, the median survival time was 281 days and the beneficial ratio 51.1% (23/45) versus 246 days and 44.4% (20/45) respectively in the control group. The inter-group comparisons of survival (P = 0.235) and curative effect (χ(2) = 0.04, P > 0.05) showed no statistical significance. In the estimated drug tolerated group (ERCC1 high expression or TOPO I low expression), the median survival time was 196 days and the beneficial ratio 4/14 versus 304 days and 51.3% (39/76) in the estimated drug sensitive group. The inter-group comparisons of survival and curative effect (both P < 0.05) had statistical significance. The median survival time and beneficial ratio significantly increased in estimated drug sensitive group than those in estimated drug tolerated group. CONCLUSIONS: The expression of drug related molecule in colorectal cancer tissue is significantly associated with curative effect in patients. Patients with down-regulated ERCC1 on Oxaliplatin or up-regulated TOPO Ion Irinotecan have longer survival and better curative effect. And chemotherapies guided by drug related molecule detection may boost curative effects in metastatic colorectal cancer.

[The level of transgelin related to the function of dendritic cells pulsed with liver cancer].

OBJECTIVE: To explore the relationships between the expression of transgelin in dendritic cells (DCs) pulsed with hepatocellular carcinoma lysates and the functions of the DCs. METHODS: DCs derived from healthy human white blood cells were divided into 3 groups: one was pulsed with high metastatic potential hepatocellular carcinoma cell line (MHCC97H) lysates, one with lysates of a low metastatic potential cell line (MHCC97L), and one un-pulsed DCs served as the control. The morphology of the DCs was observed by confocal microscopy and scanning electron microscopy. The phenotypes of the DCs were detected by flowcytometric analysis. The mixed leucocyte reaction (MLR) test and IL-12 secretion of DCs in the supernatants of MLR were employed to determine the functions of the DCs; the expression of transgelin was detected by Western blot. RESULTS: There were no morphological changes in the different DCs, but the levels of HLA-DR, CD80, CD83, CD86, MLR and IL-12 and transgelin were significantly higher in the two pulsed groups than those in the control group (P less than 0.01). In MHCC97H pulsed DCs, their CD80, CD83, CD86, and the expression of transgelin were also higher than those in the control group (P less than 0.05). The expression of transgelin was significantly higher in the MHCC97H pulsed group than in the MHCC97L loaded group, but CD80, CD83, CD86 and the level of IL-12 were all lower in the MHCC97H loaded DC group in comparison with those in the MHCC97 pulsed group (P less than 0.05). CONCLUSION: The expression of transgelin in DCs pulsed with HCC lysates is related to the functions of the DCs.

Screening and detection of portal vein tumor thrombi-associated serum low molecular weight protein biomarkers in human hepatocellular carcinoma.

PURPOSE: Serum low molecular weight protein biomarkers might be important in relation to portal vein tumor thrombi (PVTT) in hepatocellular carcinoma (HCC). This study aimed to screen and to detect these biomarkers. METHODS: We selected sera of 3 groups from 12 healthy volunteers, 12 HCC patients without PVTT and 12 HCC patients with PVTT, respectively. By using two-dimensional gel electrophoresis (2-DE) in which the first dimension was 16% SDS-PAGE, serum protein images of 3 groups were analyzed by Image Master Software. The differential protein spots were further identified by MALDI-TOF MS/MS. RESULTS: Compared with 12.5% SDS-PAGE gel, there were more protein bands between 3 and 20 kDa in 16% SDS-PAGE gel and low molecular weight (MW) protein spots (< 20 kDa) were clearly shown. Fifteen differential protein spots representing five proteins were found in the three groups by inter-class comparison and were then identified. Compared with the healthy group, apolipoprotein A-I, lipoprotein CIII, transthyretin and DNA topoisomerase II were down regulated in HCC groups while haptoglobin-2 was over expressed. All the five proteins were less in PVTT group than in non-PVTT group. CONCLUSION: The expression of low MW serum protein changes obviously in the beginning and progressive stage of HCC, and differentially expressed low MW proteins might be the potential biomarkers in early prognostication and surveillance of treatment for HCC and PVTT.

[Screening low molecular weight protein biomarkers relevant to portal vein tumor thrombi in serum of patients with hepatocellular carcinoma].

OBJECTIVE: To screen low molecular weight protein biomarkers relevant to portal vein tumor thrombi (PVTT) in serum of hepatocellular carcinoma (HCC) patients. METHODS: Serum samples were obtained from 12 healthy volunteers, 12 HCC patients without PVTT and 12 HCC patients with PVTT. Using two-dimensional gel electrophoresis (2-DE) in which the second dimension was 16% SDS-PAGE, serum protein images of the 3 groups were analyzed by ImageMaster software. The differential protein spots were further identified by MALDI-TOF MS/MS. RESULTS: Comparing the results using 12.5% SDS-PAGE gel, there were more protein bands (between 3 x 10(3) and 20 x 10(3)) and low molecular weight (MW) protein spots (less than 20 x 10(3)) were clearly shown in the 16% SDS-PAGE gel. Fifteen differential protein spots representing 5 proteins were found in the 3 groups by inter-class comparison and they were then identified. Compared with those in the healthy group, apolipoprotein A-I, lipoprotein CIII, transthyretin and DNA topoisomerase II were all down regulated in HCC groups and haptoglobin-2 was over expressed. All 5 proteins decreased more in the PVTT group than in the non-PVTT group. CONCLUSION: The expression of low MW serum protein obviously changes in the beginning and in the progressive stage of HCC, and differentially expressed low MW proteins might be potential biomarkers in an early prognostic prediction and surveillance in the treatment for HCC and PVTT.