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Background:Protein inhibitor of activated STAT 1( PIAS1 )is an important regulator for inflammatory signaling network,which is low expressed in gastric cancer and associated with development of cancer,but its mechanism has not been elucidated. Aims:To investigate the effect of PIAS1 on epithelial-mesenchymal transition( EMT)of gastric cancer under inflammatory microenvironment. Methods:Recombinant adenovirus Ad5/F35-PIAS1 and Ad5/F35-null were constructed and transfected into gastric cancer cell line SGC-7901,mRNA and protein expressions of PIAS1 were detected by RT-PCR and Western blotting,respectively. SGC-7901 cells were divided into IL-6 treatment group,Ad5/F35-PIAS1﹢IL-6 treatment group and Ad5/F35-null﹢IL-6 treatment group. Cell proliferation was measured by MTT method,migration and invasion capacities were assessed by wound healing test and Transwell chamber invasion assay. Protein expressions of E-cadherin,Snail,Twist,Vimentin and P-p38MAPK were assessed by Western blotting. Results:The transfection of Ad5/F35-PIAS1 significantly increased the expressions of PIAS1 mRNA and protein in SGC-7901 cells. Compared with IL-6 treatment group and Ad5/F35-null﹢IL-6 treatment group,capacities of cell proliferation,migration and invasion were significantly decreased(P ﹤0. 01);protein expressions of Snail,Twist,Vimentin and P-p38MAPK were significantly decreased while expression of E-cadherin protein was significantly increased in Ad5/F35-PIAS1 ﹢IL-6 treatment group ( P﹤0. 01). No significant differences in above-mentioned indices were found between IL-6 treatment group and Ad5/F35-null﹢IL-6 treatment group(P﹥0. 05). Conclusions:PIAS1 could inhibit EMT of gastric cancer cells under inflammatory microenvironment,and may play an important role in inhibition of tumor invasion and metastasis.
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Objective To explore the relationship between PIAS3 expression and the degree of malignancy of meningiomas.Methods 72 cases of different degree of malignant meningioma and 13 cases of surgical specimens of normal brain tissue were extracted the total RNA,and detected the levels of PIAS3 in different degree of meningioma and normal brain tissue through comparative control study by using real-time fluorescence quantitative PCR.Results PIAS3 was low expressed in normal brain tissue,however,high expressed in the human brain meningioma with significant differences(P＜0.01).There were also significant differences found in expression level of PIAS3 between meningiomas grade I and Ⅱ,or Ⅲ level(P＜0.05),but the differences between meningiomas grade Ⅱ and Ⅲ were not obvious(P＞0.05).And PIAS3 expression was not related with the depth of infiltration in invasive meningiomas(P＞0.05).Conclusion PIAS3 was overexpression in meningiomas,and was be closely related to the occurrence and development of meningiomas.
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Objective To study the effect of oxymatrine on p-STAT3 and PIAS3 signaling molecule and it's mRNA expression in the proliferation of the human mesangial cells (HMCs) induced by lipopolysaccharide(LPS) and to explore their relationship. Methods HMCs were divided into three groups: control group, LPS group and oxymatrine group. HMC proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay. Type Ⅳ collagen in the supernatants of the cultured HMCs was detected by ELISA at 12, 24, 48 hours respectively. At the same time, the protein and mRNA expressions of p-STAT3 and PIAS3 were measured by Western blot and real-time quantitative RT-PCR. Results The cell proliferation, the mRNA and protein expression of type Ⅳ collagen, p-STAT3 in LPS group were increased compared with the control group (P<0.01), but they were decreased in oxymatrine group (P < 0.01). The expressions of protein and mRNA of PIAS3 in LPS group were decreased significantly compared with control group (P<0.01), but they were increased in oxymatrine group (P<0.01). Conclusion Oxymatrine can down-regulate the expression of p-STAT3 and up-regulate the expression of PIAS3, which plays an important role in the process of LPS-induced HMCs proliferation.
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Zinc finger protein 133 (ZNF133) is composed of a Kruppel-associated box (KRAB) domain and 14 contiguous zinc finger motifs. ZNF133 is regarded as a transcriptional repressor because the KRAB domain has potent repressor activity and the zinc finger motifs usually act in binding to DNA. However, we found that the zinc finger motifs of ZNF133 also possessed transcriptional repressor activity. By two-hybrid screening assay, we found that the zinc finger motifs of ZNF133 interacted with protein inhibitor of activated STAT1 (PIAS1). PIAS1 enhanced the transcriptional repression activity of ZNF133 through the zinc finger motifs. This effect of PIAS1 was relieved by an inhibitor of the histone deacetylases (HDACs). These results demonstrate that the transcriptional repressor activity of ZNF133 is regulated by both the KRAB domain and the zinc finger motifs, and that the repressive effect by zinc finger motifs is mediated by PIAS1.