目的:探讨miR-101与miR-25在胃癌术前术后血清中的表达及其与病理因素间的关系,探讨其是否能作为胃癌早期诊断的新型生物标志物.方法:应用实时荧光定量(PCR)检测58例胃癌(其中31例配对胃癌术前术后),30例胃癌癌前病变,30例正常对照血清m...目的:探讨miR-101与miR-25在胃癌术前术后血清中的表达及其与病理因素间的关系,探讨其是否能作为胃癌早期诊断的新型生物标志物.方法:应用实时荧光定量(PCR)检测58例胃癌(其中31例配对胃癌术前术后),30例胃癌癌前病变,30例正常对照血清miR-101与miR-25的相对表达量,比较miR-101与miR-25在胃癌术前术后表达差异,及其与病理参数的关系,绘制研究对象工作特征曲线(ROC),评估血清miR-101与miR-25对胃癌的临床诊断价值.结果:胃癌血清miR-101表达水平显著性低于正常对照组(P<0.01)及胃癌癌前病变组(P<0.01),而胃癌血清miR-25(P<0.01)表达水平显著升高.胃癌术后血清miR-101表达水平明显高于术前(P=0.007),而血清miR-25在胃癌术后显著性降低(P=0.011).ROC曲线分析显示血清miR-101与miR-25对胃癌诊断价值较高[miR-101:ROC曲线下面积(Area Under roc Curve,AUC)=0.857,敏感度=0.710,特异度=0.881;miR-25:AUC=0.821,敏感度=0.702,特异度=0.800],而血清miR-101与miR-25联合诊断胃癌的AUC为0.905,其敏感性和特异性分别为75.9%和86.7%.进一步分析发现胃癌血清miR-101低表达与幽门螺旋杆菌(helicobacter pylori,Hp)感染有关,miR-101表达水平在感染HP的胃癌血清中显著低于未感染HP的胃癌血清(P=0.012);胃癌血清miR-101低表达与胃癌淋巴结转移(P=0.033)和临床分期(P=0.015)显著相关;胃癌血清miR-25在高临床分期(P=0.018)和淋巴结转移(P<0.001)表达水平升高.结论:血清miR-101与miR-25可能作为胃癌术前术后动态监测和胃癌诊断的新型潜在标志物.展开更多
Emerging evidence has indicated that circular RNAs（circRNAs） play pivotal roles in the regulation of cellular processes and are found to be aberrantly expressed in a variety of tumors. However, the clinical role of ...Emerging evidence has indicated that circular RNAs（circRNAs） play pivotal roles in the regulation of cellular processes and are found to be aberrantly expressed in a variety of tumors. However, the clinical role of circ RNAs in bladder cancer（BC） and the molecular mechanisms have yet to be fully understood. In this study, the clinical specimens were obtained and the expression level of a circ RNA BCRC4 was detected by real-time PCR in both BC tissues and cell line. The circular RNA over-expression plasmid was constructed and transfected into BC cells and related cell line. The cell cycles and apoptosis were observed using inverted microscope and flow cytometry. Western blotting was used to compare the relative protein expression of groups with different treatments. It was found that circ RNA BCRC4 expression was lower in BC tissues than in adjacent normal tissues. Furthermore, consequences of forced-expression of BCRC4 promoted apoptosis and inhibited viability of T24T and UMUC3 cells, and up-regulated BCRC4-increased miR-101 level, which suppressed EZH2 expression in both RNA and protein levels. In addition, gambogic acid（GA） is a promising natural anticancer compound for BC therapy, and GA treatment increased the BCRC4 expression in T24T and UMUC3 cells in a dose-dependent manner. Altogether, our findings suggest that BCRC4 functions as a tumor suppressor in BC, and mediates anticancer function, at least in part, by up-regulating the expression of miR-101. Targeting this newly identified circ RNA may help us develop a novel strategy for treating human BC.展开更多
Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition(EMT), during which cells dedifferentiate from a relative...Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition(EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas(TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This "paradox" can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating m RNA and micro RNA(mi RNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major mi RNAs and 214 m RNAs. Among the 8 mi RNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 mi RNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer.展开更多
文摘目的:探讨miR-101与miR-25在胃癌术前术后血清中的表达及其与病理因素间的关系,探讨其是否能作为胃癌早期诊断的新型生物标志物.方法:应用实时荧光定量(PCR)检测58例胃癌(其中31例配对胃癌术前术后),30例胃癌癌前病变,30例正常对照血清miR-101与miR-25的相对表达量,比较miR-101与miR-25在胃癌术前术后表达差异,及其与病理参数的关系,绘制研究对象工作特征曲线(ROC),评估血清miR-101与miR-25对胃癌的临床诊断价值.结果:胃癌血清miR-101表达水平显著性低于正常对照组(P<0.01)及胃癌癌前病变组(P<0.01),而胃癌血清miR-25(P<0.01)表达水平显著升高.胃癌术后血清miR-101表达水平明显高于术前(P=0.007),而血清miR-25在胃癌术后显著性降低(P=0.011).ROC曲线分析显示血清miR-101与miR-25对胃癌诊断价值较高[miR-101:ROC曲线下面积(Area Under roc Curve,AUC)=0.857,敏感度=0.710,特异度=0.881;miR-25:AUC=0.821,敏感度=0.702,特异度=0.800],而血清miR-101与miR-25联合诊断胃癌的AUC为0.905,其敏感性和特异性分别为75.9%和86.7%.进一步分析发现胃癌血清miR-101低表达与幽门螺旋杆菌(helicobacter pylori,Hp)感染有关,miR-101表达水平在感染HP的胃癌血清中显著低于未感染HP的胃癌血清(P=0.012);胃癌血清miR-101低表达与胃癌淋巴结转移(P=0.033)和临床分期(P=0.015)显著相关;胃癌血清miR-25在高临床分期(P=0.018)和淋巴结转移(P<0.001)表达水平升高.结论:血清miR-101与miR-25可能作为胃癌术前术后动态监测和胃癌诊断的新型潜在标志物.
文摘Emerging evidence has indicated that circular RNAs（circRNAs） play pivotal roles in the regulation of cellular processes and are found to be aberrantly expressed in a variety of tumors. However, the clinical role of circ RNAs in bladder cancer（BC） and the molecular mechanisms have yet to be fully understood. In this study, the clinical specimens were obtained and the expression level of a circ RNA BCRC4 was detected by real-time PCR in both BC tissues and cell line. The circular RNA over-expression plasmid was constructed and transfected into BC cells and related cell line. The cell cycles and apoptosis were observed using inverted microscope and flow cytometry. Western blotting was used to compare the relative protein expression of groups with different treatments. It was found that circ RNA BCRC4 expression was lower in BC tissues than in adjacent normal tissues. Furthermore, consequences of forced-expression of BCRC4 promoted apoptosis and inhibited viability of T24T and UMUC3 cells, and up-regulated BCRC4-increased miR-101 level, which suppressed EZH2 expression in both RNA and protein levels. In addition, gambogic acid（GA） is a promising natural anticancer compound for BC therapy, and GA treatment increased the BCRC4 expression in T24T and UMUC3 cells in a dose-dependent manner. Altogether, our findings suggest that BCRC4 functions as a tumor suppressor in BC, and mediates anticancer function, at least in part, by up-regulating the expression of miR-101. Targeting this newly identified circ RNA may help us develop a novel strategy for treating human BC.
基金supported by the U.S. National Institutes of Health grants (U24 CA143835 to IS and WZ, P50 CA083639 and P50 CA098258 to AKS)MD Anderson support grant (CA016672) to WZ+6 种基金a grant from the Blanton-Davis Ovarian Cancer Research Program to WZgrants from the Program for Changjiang Scholars, Innovative Research Team in University (PCSIRT) in Chinathe National Key Scientifi c and Technological Project (2011ZX0 9307-001-04)Tianjin Science and Technology Committee Foundation (09ZCZDSF04700) to KCa grant from National Nature Science Foundation of China (#81201651) to YSa grant from Fondazione CARIPLO (2013-0865) to DMthe A. Lavoy Moore Endowment Fund to YS and DY
文摘Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition(EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas(TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This "paradox" can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating m RNA and micro RNA(mi RNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major mi RNAs and 214 m RNAs. Among the 8 mi RNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 mi RNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer.
