STAT2是信号转导和转录激活因子(signal transducers and activators of transcription,STAT)家族中的一员,它被激活后转入细胞核内与特异性DNA结合,影响基因转录,参与细胞的生长、分化、生存和凋亡。重要的是,目前研究表明,STAT2基因...STAT2是信号转导和转录激活因子(signal transducers and activators of transcription,STAT)家族中的一员,它被激活后转入细胞核内与特异性DNA结合,影响基因转录,参与细胞的生长、分化、生存和凋亡。重要的是,目前研究表明,STAT2基因缺失或过表达对肿瘤发生发展有着重要影响,与肿瘤血管生成、肿瘤增殖及肿瘤凋亡密切相关,并且在肿瘤的干扰素治疗中扮演着重要角色。本文就STAT2与肿瘤研究进展做一综述。展开更多
Objective:To measure the expression pattern of STAT2 in cenical cancer initiation and progression in tissue sections from patients with cervicitis,dysplasia,and cenical cancer. Methods:Antibody against human STAT2 was...Objective:To measure the expression pattern of STAT2 in cenical cancer initiation and progression in tissue sections from patients with cervicitis,dysplasia,and cenical cancer. Methods:Antibody against human STAT2 was confirmed by plasmids transient transfection and Western blot Immunohistochemistry was used to delect STAT2 expression in the cervical biopsies by using the confirmed antibody against STAT2 as the primary antibody.Results:It was found that the overall rate of positive STAT2 expression in the cervicitis,dysplasia and cenical cancer groups were 38.5%,69.49%and 76.991,respectively.The STAT2 levels are significantly increased in premalignant dysplasia and cervical cancer,as compared lo cervicitis(P【 0.05). Noticeably,STAT2 signals were mainly found in the cytoplasm,implying that STAT2 was not biologically active.Conclusions:These findings reveal an association between cenical cancer progression and augmented STAT2 expression.In conclusion.STAT2 increase appears to be an early detectable cellular event in cenical cancer development.展开更多
Although much progress has been made in identifying the signaling pathways that mediate viral RNA-induced apoptosis and activation of interferon-stimulated genes, the role that bacterial RNA plays in regulating these ...Although much progress has been made in identifying the signaling pathways that mediate viral RNA-induced apoptosis and activation of interferon-stimulated genes, the role that bacterial RNA plays in regulating these responses has remained undetermined. Herein, we identified bacterial RNA as a novel inducer of the apoptotic cell death. Unlike the parental cells, STAT1 and STAT2 mutants display apoptotic defects which were reversed by restoring the expression of wild type proteins. While STAT1 mutants lacking tyrosine-701 or a functional SH2 domain were effective as the wild-type protein in restoring the apoptotic response, the mutant carrying a point mutation at serine-727 of STAT1 was resistant to bacterial RNA-induced apoptosis. We also determined that the lack of apoptosis in the STAT1 and STAT2 mutants was correlated with the constitutive and inducible activation of apoptosis regulating proteins. Furthermore, we show that bacterial RNA induces transcriptional activation of STAT1, STAT2, IRF1, and ISGF3, which was impaired in STAT1 or STAT2 mutants. These observations suggested that the participation of STATs in regulating the apoptotic response is independent of their downstream functions as cytokine-induced transcriptional activators. In addition to bacterial immunity, the results presented here may also have implications in cellular pathophysiology and RNA-based therapy.展开更多
目的研究慢性丙型病毒性肝炎患者外周血单核细胞(PBMC)中2’,5’寡腺苷酸合成酶(2’,5’-Oligoadenylate synthetase,2-5AS)的表达及其传导与转录激活因子(Signal transducer and activator of transcription,Stat)Stat1和Stat2等的水...目的研究慢性丙型病毒性肝炎患者外周血单核细胞(PBMC)中2’,5’寡腺苷酸合成酶(2’,5’-Oligoadenylate synthetase,2-5AS)的表达及其传导与转录激活因子(Signal transducer and activator of transcription,Stat)Stat1和Stat2等的水平相关性分析。方法选择60例慢性丙肝患者,抽取外周血分离PBMC。首先测定每份标本的2-5AS活性。然后将所有丙肝患者的PBMC标本按按编号单双数分为对照组和实验组,进行体外培养。其中,对照组PBMC不添加干扰素α(interferon alpha,IFN-α),而实验组PBMC添加1000IU/ml IFN-α。体外培养大约24小时后,测定PBMC中2-5AS活性、Stat1和Stat2等的表达量。结果和对照组相比,实验组PBMC的2-5AS活性明显升高(P<0.05)。实验组PBMC中,在2-5AS活性增高的同时,Stat1和Stat2等表达量也呈现明显增多的趋势(P<0.05)。结论基础的2-5AS活性与加入IFNα刺激培养后Stat1的改变幅度呈负相关(P<0.05);2-5AS基础水平和IFNα刺激后的Stat2表达的变化没有相关性(P>0.05)。展开更多
Background:Circular RNAs(circRNAs)generated by back-splicing of precursor mRNAs(pre-mRNAs)are often aberrantly expressed in cancer cells.Accumulating evidence has revealed that circRNAs play a critical role in the pro...Background:Circular RNAs(circRNAs)generated by back-splicing of precursor mRNAs(pre-mRNAs)are often aberrantly expressed in cancer cells.Accumulating evidence has revealed that circRNAs play a critical role in the progression of several cancers,including colorectal cancer(CRC).However,the current understandings of the emerging functions of circRNAs in CRC lipid metabolism and the underlying molecular mechanisms are still limited.Here,we aimed to explore the role of circCAPRIN1 in regulating CRC lipid metabolism and tumorigenesis.Methods:circRNA microarray was performed with three pairs of tumor and non-tumor tissues from CRC patients.The expression of circRNAs were determined by quantitative PCR(qPCR)and in situ hybridization(ISH).The endogenous levels of circRNAs in CRC cells were manipulated by transfection with lentiviruses overexpressing or silencing circRNAs.The regulatory roles of circRNAs in the occurrence of CRC were investigated both in vitro and in vivo using gene expression array,RNA pull-down/mass spectrometry,RNA immunoprecipitation assay,luciferase reporter assay,chromatin immunoprecipitation analysis,and fluorescence in situ hybridization(FISH).Results:Among circRNAs,circCAPRIN1 was most significantly upregulated in CRC tissue specimens.circCAPRIN1 expression was positively correlated with the clinical stage and unfavorable prognosis of CRC patients.Downregulation of circCAPRIN1 suppressed proliferation,migration,and epithelial-mesenchymal transition of CRC cells,while circCAPRIN1 overexpression had opposite effects.RNA sequencing and gene ontology analysis indicated that circCAPRIN1 upregulated the expressions of genes involved in CRC lipid metabolism.Moreover,circCAPRIN1 promoted lipid synthesis by enhancing Acetyl-CoA carboxylase 1(ACC1)expression.Further mechanistic assays demonstrated that circCAPRIN1 directly bound signal transducer and activator of transcription 2(STAT2)to activate ACC1 transcription,thus regulating lipid metabolism and facilitating CRC tumorigenesis.Conclusions:These findings revealed the oncogenic role and mechanism of circCAPRIN1 in CRC.circCAPRIN1 interacted with STAT2 to promote CRC tumor progression and lipid synthesis by enhancing the expression of ACC1.circCAPRIN1 may be considered as a novel potential diagnostic and therapeutic target for CRC patients.展开更多
目的研究通痹颗粒对胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠铁调素(hepcidin,Hepc)、Janus激酶(janus kinase,JAK)2/信号转导子和转录激活子(signal transduction and activator of transcription,STAT)3信号通路的影响...目的研究通痹颗粒对胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠铁调素(hepcidin,Hepc)、Janus激酶(janus kinase,JAK)2/信号转导子和转录激活子(signal transduction and activator of transcription,STAT)3信号通路的影响。方法选取36只雌性SD大鼠随机分成空白组、模型组、阳性对照组和通痹颗粒低、中、高剂量组,每组6只。空白组不予处理,其余组用牛Ⅱ型胶原建立CIA模型。造模完成后,空白组、模型组予生理盐水灌胃,其余各组分别以巴瑞替尼片和低、中、高剂量通痹颗粒灌胃。每天1次,连续4周。HE染色行滑膜组织病理学观察;酶联免疫吸附法测定血清Hepc、白细胞介素6(interleukin 6,IL-6)水平;逆转录-聚合酶链反应法测定滑膜中JAK2、STAT3、细胞信号因子传导抑制体(suppressor of cytokine signaling,SOCS)1、SOCS3的mRNA相对表达量;Western blot法检测滑膜中JAK2、p-JAK2、STAT3、p-STAT3、SOCS1、SOCS3的蛋白表达量。结果模型组见滑膜上皮结构缺损,滑膜重度增生,排列紊乱,并有大量炎症细胞浸润和多个血管翳形成;各给药组滑膜炎症均有所减轻,阳性对照组优于通痹颗粒高剂量组,通痹颗粒中、高剂量组优于低剂量组。与模型组相比,各给药组关节炎指数评分、血清Hepc和IL-6水平均显著降低(P<0.01);与阳性对照组相比,通痹颗粒中、低剂量组关节炎指数评分、血清Hepc和IL-6水平均升高(P<0.05)。与模型组比较,阳性对照组和通痹颗粒低、中、高剂量组JAK2、STAT3 mRNA和蛋白以及p-JAK2、p-STAT3的蛋白表达量均降低(P<0.05),而通路抑制因子SOCS1、SOCS3 mRNA和蛋白的表达均升高(P<0.05);与阳性对照组比较,通痹颗粒各剂量组JAK2、STAT3 mRNA和蛋白以及p-JAK2、p-STAT3的蛋白表达量均升高(P<0.05),而SOCS1、SOCS3 mRNA和蛋白的表达均降低(P<0.05)。结论通痹颗粒能够改善CIA大鼠滑膜炎症,其机制可能与抑制JAK2/STAT3信号通路而减少Hepc的表达有关。展开更多
文摘STAT2是信号转导和转录激活因子(signal transducers and activators of transcription,STAT)家族中的一员,它被激活后转入细胞核内与特异性DNA结合,影响基因转录,参与细胞的生长、分化、生存和凋亡。重要的是,目前研究表明,STAT2基因缺失或过表达对肿瘤发生发展有着重要影响,与肿瘤血管生成、肿瘤增殖及肿瘤凋亡密切相关,并且在肿瘤的干扰素治疗中扮演着重要角色。本文就STAT2与肿瘤研究进展做一综述。
基金funded by 'Chinese National Nature Science Foundation(30771122)''Chinese Ministry of Education,Research Start-up Funding for Home Smdents' to Ming Li
文摘Objective:To measure the expression pattern of STAT2 in cenical cancer initiation and progression in tissue sections from patients with cervicitis,dysplasia,and cenical cancer. Methods:Antibody against human STAT2 was confirmed by plasmids transient transfection and Western blot Immunohistochemistry was used to delect STAT2 expression in the cervical biopsies by using the confirmed antibody against STAT2 as the primary antibody.Results:It was found that the overall rate of positive STAT2 expression in the cervicitis,dysplasia and cenical cancer groups were 38.5%,69.49%and 76.991,respectively.The STAT2 levels are significantly increased in premalignant dysplasia and cervical cancer,as compared lo cervicitis(P【 0.05). Noticeably,STAT2 signals were mainly found in the cytoplasm,implying that STAT2 was not biologically active.Conclusions:These findings reveal an association between cenical cancer progression and augmented STAT2 expression.In conclusion.STAT2 increase appears to be an early detectable cellular event in cenical cancer development.
文摘Although much progress has been made in identifying the signaling pathways that mediate viral RNA-induced apoptosis and activation of interferon-stimulated genes, the role that bacterial RNA plays in regulating these responses has remained undetermined. Herein, we identified bacterial RNA as a novel inducer of the apoptotic cell death. Unlike the parental cells, STAT1 and STAT2 mutants display apoptotic defects which were reversed by restoring the expression of wild type proteins. While STAT1 mutants lacking tyrosine-701 or a functional SH2 domain were effective as the wild-type protein in restoring the apoptotic response, the mutant carrying a point mutation at serine-727 of STAT1 was resistant to bacterial RNA-induced apoptosis. We also determined that the lack of apoptosis in the STAT1 and STAT2 mutants was correlated with the constitutive and inducible activation of apoptosis regulating proteins. Furthermore, we show that bacterial RNA induces transcriptional activation of STAT1, STAT2, IRF1, and ISGF3, which was impaired in STAT1 or STAT2 mutants. These observations suggested that the participation of STATs in regulating the apoptotic response is independent of their downstream functions as cytokine-induced transcriptional activators. In addition to bacterial immunity, the results presented here may also have implications in cellular pathophysiology and RNA-based therapy.
文摘目的研究慢性丙型病毒性肝炎患者外周血单核细胞(PBMC)中2’,5’寡腺苷酸合成酶(2’,5’-Oligoadenylate synthetase,2-5AS)的表达及其传导与转录激活因子(Signal transducer and activator of transcription,Stat)Stat1和Stat2等的水平相关性分析。方法选择60例慢性丙肝患者,抽取外周血分离PBMC。首先测定每份标本的2-5AS活性。然后将所有丙肝患者的PBMC标本按按编号单双数分为对照组和实验组,进行体外培养。其中,对照组PBMC不添加干扰素α(interferon alpha,IFN-α),而实验组PBMC添加1000IU/ml IFN-α。体外培养大约24小时后,测定PBMC中2-5AS活性、Stat1和Stat2等的表达量。结果和对照组相比,实验组PBMC的2-5AS活性明显升高(P<0.05)。实验组PBMC中,在2-5AS活性增高的同时,Stat1和Stat2等表达量也呈现明显增多的趋势(P<0.05)。结论基础的2-5AS活性与加入IFNα刺激培养后Stat1的改变幅度呈负相关(P<0.05);2-5AS基础水平和IFNα刺激后的Stat2表达的变化没有相关性(P>0.05)。
基金National Natural Science Foundation of China,Grant/Award Numbers:81972260,82103259Shanghai Municipal Natural Science Foundation,Grant/Award Number:21ZR1414400Shanghai Medical Innovation Research Project,Grant/Award Number:22Y11907600。
文摘Background:Circular RNAs(circRNAs)generated by back-splicing of precursor mRNAs(pre-mRNAs)are often aberrantly expressed in cancer cells.Accumulating evidence has revealed that circRNAs play a critical role in the progression of several cancers,including colorectal cancer(CRC).However,the current understandings of the emerging functions of circRNAs in CRC lipid metabolism and the underlying molecular mechanisms are still limited.Here,we aimed to explore the role of circCAPRIN1 in regulating CRC lipid metabolism and tumorigenesis.Methods:circRNA microarray was performed with three pairs of tumor and non-tumor tissues from CRC patients.The expression of circRNAs were determined by quantitative PCR(qPCR)and in situ hybridization(ISH).The endogenous levels of circRNAs in CRC cells were manipulated by transfection with lentiviruses overexpressing or silencing circRNAs.The regulatory roles of circRNAs in the occurrence of CRC were investigated both in vitro and in vivo using gene expression array,RNA pull-down/mass spectrometry,RNA immunoprecipitation assay,luciferase reporter assay,chromatin immunoprecipitation analysis,and fluorescence in situ hybridization(FISH).Results:Among circRNAs,circCAPRIN1 was most significantly upregulated in CRC tissue specimens.circCAPRIN1 expression was positively correlated with the clinical stage and unfavorable prognosis of CRC patients.Downregulation of circCAPRIN1 suppressed proliferation,migration,and epithelial-mesenchymal transition of CRC cells,while circCAPRIN1 overexpression had opposite effects.RNA sequencing and gene ontology analysis indicated that circCAPRIN1 upregulated the expressions of genes involved in CRC lipid metabolism.Moreover,circCAPRIN1 promoted lipid synthesis by enhancing Acetyl-CoA carboxylase 1(ACC1)expression.Further mechanistic assays demonstrated that circCAPRIN1 directly bound signal transducer and activator of transcription 2(STAT2)to activate ACC1 transcription,thus regulating lipid metabolism and facilitating CRC tumorigenesis.Conclusions:These findings revealed the oncogenic role and mechanism of circCAPRIN1 in CRC.circCAPRIN1 interacted with STAT2 to promote CRC tumor progression and lipid synthesis by enhancing the expression of ACC1.circCAPRIN1 may be considered as a novel potential diagnostic and therapeutic target for CRC patients.
