Prognostic significance of high expression of thrombospondin 2 in pancreatic cancer and its effect on proliferation and migration of cancer cells / 中国肿瘤生物治疗杂志

@# Objective:To explore the prognostic significance of thrombospondin 2 (THBS2) expression and its effects on the proliferation and migration of pancreatic cancerASPC-1 cells for patients with pancreatic cancer, and to investigate its possible molecular mechanism. Methods: The expression of THBS2 in pancreatic cancer tissues and its effects on overall survival rate in patients were analyzed by online database. THBS2 expression in pancreatic cancerASPC-1 cells was detected by Western Blotting; RNAinterference was used to knockdown the expression of THBS2 inASPC-1 cells, and then the effects of THBS2 knockdown on cell proliferation and migration were detected by MTT and Transwell assays, while its effects on protein expression levels (MMP, E-cadherin,AKT and PI3K) were detected by Wb. Results: Expression of THBS2 in pancreatic cancer tissues was significantly higher than that in normal pancreatic tissues (P<0.01), and the high expression of THBS2 could lead to the decrease of overall survival rate in pancreatic cancer patients. The expression of THBS2 in pancreatic cancer cell lines was significantly up-regulated; however, after interference on the expression of THBS2, the proliferation (P<0.01) and migration ability (P<0.01) of ASPC-1 cells were significantly decreased, and the expression of AKT and PI3K in cells was significantly down-regulated (P<0.01). Conclusion: THBS2 is highly expressed in pancreatic cancer tissues and cells, and is negatively correlated with the prognosis of patients. The mechanism is possibly related with the proliferation and migration of ASPC-1 cells that regulated byAKT/PI3K signaling pathway.

Differential expression and methylation of integrin subunit alpha 11 and thrombospondin in the amnion of preterm birth

OBJECTIVE: This study aimed to investigate the association between preterm birth and epigenetic mechanisms in the amnion. METHODS: We examined the association between differentially methylated regions (DMRs) and differentially expressed genes (DEG) using a cytosine-phosphate-guanine methylation array and whole-transcriptome sequencing from the amnion (preterm birth, n=5; full term, n=5). We enrolled 35 participants for mRNA expression analysis and pyrosequencing: 16 full-term and 19 preterm subjects. We compared the association of integrin subunit alpha 11 (ITGA11) and thrombospondin 2 (THBS2) gene methylation status with mRNA expression in the amnion. RESULTS: In the preterm birth group, methylation of ITGA11 and THBS2 genes was significantly lower (ITGA11 gene: 60.30% vs. 73.16%, P < 0.05; THBS2 gene: 64.59% vs. 73.16%, P < 0.05), and the expression of the genes was significantly higher than that in the full-term group (ITGA11 gene: 14.20 vs. 1.57, P < 0.01; THBS2 gene: 1.18 vs. 10.34, P < 0.05). CONCLUSION: Methylation of the ITGA11 and THBS2 genes in the amnion was associated with preterm birth. Thus, ITGA11 and THBS2 gene methylation status in the amnion may be valuable in explaining the mechanism underlying preterm birth.

Effects of miR-1246 on proliferation,invasion and migration of cervical squamous cell carcinoma cell line SiHa and its target gene / 西安交通大学学报(医学版)

ABSTRACT:Objective To explore the effects of miRNA-1246 (miR-1246)on cell proliferation,invasion and migration in human cervical squamous cell carcinoma (CSCC)cell line SiHa.Methods SiHa cells were assigned into 3 groups:miR-1246 analog group,miR-1246 antagonist group and control group.Transfection efficiency was determined.The MTT assay,transwell assay and wound healing assay were performed respectively to evaluate the proliferation,invasion and migration abilities of SiHa cells.Western blot was carried out to detect the expression of thrombospondin-2 (THBS2)before and after transfection.A THBS2 3’-UTR-containing dual luciferase plasmid was synthesized and co-transfected with miR-1246 into SiHa cells to observe the luciferase enzyme activity.Results MTT assay,transwell assay and wound healing assay revealed that the abilities of proliferation,migration and invasion were significantly enhanced (P<0.01)in SiHa cells transfected with miR-1246 analog,but suppressed in SiHa cells transfected with miR-1246 antagonist.Western blot showed that SiHa cells transfected with miR-1246 analog had significantly decreased THBS2 expression (gray value = 6 .2 8 ± 1 0 .2 2 , P=0 .0 1 3 ) while those transfected with miR-1246 antagonist had significantly increased THBS2 expression (gray value = 12.90±19.81, P=0.037).After co-transfected with miR-1246 and THBS2 3’-UTR-containing plasmid,SiHa cells exhibited a decreased level of luciferase enzyme expression.Conclusion miR-1246 promoted the proliferation,invasion and migration of CSCC SiHa cell, and it might promote CSCC tumorigenesis and progression by suppressing the expression of its target gene THBS2 .

Clinical significance of thrombospondin-2 expression in gastric car-cinoma / 中国肿瘤临床

Objective:To investigate the clinical significance of thrombospondin-2 (THBS2) mRNA expression in gastric carcino-ma and its relationships with clinicopathologic features, microvessel density (MVD), and matrix metalloproteinase-2 (MMP-2). Meth-ods:THBS2 mRNA expression was detected in 82 cases of gastric carcinomas and adjacent tissues using real-time quantitative fluores-cence polymerase chain reaction. The correlation of this expression with clinicopathologic features was also analyzed. Cluster of differ-entiation 34 (CD34) and MMP-2 protein expression was examined using an immunohistochemical Elivision method. MVD was deter-mined based on CD34-positive tubular structures. Results:The THBS2 mRNA expression level was significantly higher in the gastric carcinomas than in paraneoplastic tissues (P=0.002). The expression was associated with the depth of tumor invasion, MVD, and MMP-2 (P=0.02, r=0.35, P<0.01, and P=0.004, respectively) but not with patient gender, patient age, tumor size, histological type, and lymph node metastasis (P=0.53, P=0.53, P=0.21, P=0.84, and P=0.96, respectively). Conclusions: THBS2 may be significantly in-volved in the occurrence and progression of gastric carcinoma. The effects of THBS2 on gastric tumor growth and metastasis can be monitored by controlling the MMP-2 expression in the carcinoma. However, the specific functions and underlying mechanisms of TH-BS2 require further investigation.