AIM:To reveal the functions of micro RNAs(mi RNAs) with respect to hepatic stellate cells(HSCs) in response to portal hypertension.METHODS:Primary rat HSCs were exposed to static water pressure(10 mm Hg,1 h) and the p...AIM:To reveal the functions of micro RNAs(mi RNAs) with respect to hepatic stellate cells(HSCs) in response to portal hypertension.METHODS:Primary rat HSCs were exposed to static water pressure(10 mm Hg,1 h) and the pressureinduced mi RNA expression profile was detected by next-generation sequencing. Quantitative real-time polymerase chain reaction was used to verify the expression of mi RNAs. A potential target of Mi R-9a-5p was measured by a luciferase reporter assay and Western blot. CCK-8 assay and Transwell assay were used to detect the proliferation and migration of HSCs under pressure.RESULTS:According to the profile,the expression of mi R-9a-5p was further confirmed to be significantly increased after pressure overload in HSCs(3.70 ± 0.61 vs 0.97 ± 0.15,P = 0.0226),which resulted in the proliferation,migration and activation of HSCs. In vivo,the up-regulation of mi R-9a-5p(2.09 ± 0.91 vs 4.27 ± 1.74,P = 0.0025) and the down-regulation of Sirt1(2.41 ± 0.51 vs 1.13 ± 0.11,P = 0.0006) were observed in rat fibrotic liver with portal hypertension. Sirt1 was a potential target gene of mi R-9a-5p. Through restoringthe expression of Sirt1 in mi R-9a-5p transfected HSCs on pressure overload,we found that overexpression of Sirt1 could partially abrogate the mi R-9a-5p mediated suppression of the proliferation,migration and activation of HSCs. CONCLUSION:Our results suggest that during liver fibrosis,portal hypertension may induce the proliferation,migration and activation of HSCs through the up-regulation of mi R-9a-5p,which targets Sirt1.展开更多
The mechanism of health effects caused by organohalogen pollutants, e.g., toxins from electronic waste(e-waste), is poorly understood. We supposed that micro RNAs(mi RNAs), an important post-transcriptional regulator,...The mechanism of health effects caused by organohalogen pollutants, e.g., toxins from electronic waste(e-waste), is poorly understood. We supposed that micro RNAs(mi RNAs), an important post-transcriptional regulator, could play a role in this process. In this study, fasting peripheral blood samples were collected from residents living at an e-waste site in northern China and a nearby reference population. Concentrations of e-waste related organohalogen pollutants in plasma from the exposure group were higher than the corresponding measurement in the reference group. Correspondingly, sixty mi RNAs in plasma showed > 2-fold change between the two groups in microarray analysis. Among them, mi R-125a-5p was confirmed to be upregulated by q RT-PCR and its validated targets were enriched in responses to xenobiotics and cancer related pathways. Furthermore, significant positive correlations were found between levels of mi R-125a-5p in plasma and reactive oxygen species(ROS) in polymorphonuclear neutrophil leukocytes(P < 0.05). These evidences suggested oxidative stress might be an intermediate between e-waste related POPs exposure and alteration of plasma mi RNA.展开更多
目的探讨结肠癌组织中长链非编码RNA(lncRNA)肿瘤蛋白翻译调节因子1(TPT1)-反义RNA1(AS1)、微小RNA(miR)-30c-5p的表达及与病理特征、预后的关系。方法选取2015年1月至2017年12月深圳大学附属第一医院收治的117例接受根治性或姑息性手...目的探讨结肠癌组织中长链非编码RNA(lncRNA)肿瘤蛋白翻译调节因子1(TPT1)-反义RNA1(AS1)、微小RNA(miR)-30c-5p的表达及与病理特征、预后的关系。方法选取2015年1月至2017年12月深圳大学附属第一医院收治的117例接受根治性或姑息性手术切除结肠癌患者,均行手术切除结肠癌组织及癌旁组织。采用qRT-PCR检测lncRNA TPT1-AS1、miR-30c-5p表达水平,分析lncRNA TPT1-AS1、miR-30c-5p表达水平与结肠癌病理特征的关系,采用Pearson相关性检验分析结肠癌组织中lncRNA TPT1-AS1与miR-30c-5p表达水平的相关性,Kaplan-Meier曲线绘制不同lncRNA TPT1-AS1、miR-30c-5p表达水平结肠癌患者3年累积生存率,Cox回归分析结肠癌患者预后影响因素。结果结肠癌组织中lncRNA TPT1-AS1表达水平明显高于癌旁组织(3.405±0.555 vs 1.766±0.096),miR-30c-5p表达水平(0.306±0.146 vs 0.872±0.267)明显低于癌旁组织(P<0.05)。结肠癌lncRNA TPT1-AS1表达水平TNM分期Ⅲ~Ⅳ期明显高于Ⅰ~Ⅱ期(3.651±0.579 vs 3.257±0.486),浸润深度T_(3)~T_(4)明显高于T_(1)~T_(2)(3.523±0.601 vs 3.301±0.491),有淋巴结转移明显高于无淋巴结转移(3.614±0.585 vs 3.220±0.456),差异均有统计学意义(P<0.05);miR-30c-5p表达水平TNM分期Ⅲ~Ⅳ期明显低于Ⅰ~Ⅱ期(0.251±0.126 vs 0.346±0.145),浸润深度T_(3)~T_(4)明显低于T_(1)~T_(2)(0.270±0.119 vs 0.338±0.162),有淋巴结转移明显低于无淋巴结转移(0.255±0.125 vs 0.351±0.151),差异均有统计学意义(P<0.05)。Pearson相关性分析显示,结肠癌组织中lncRNA TPT1-AS1与miR-30c-5p表达水平呈负相关(r=-0.572,P<0.05)。Kaplan-Meier生存曲线显示,lncRNA TPT1-AS1高表达水平组3年累积生存率明显低于低表达水平组(59.32%vs 87.93%),miR-30c-5p高表达水平组3年累积生存率明显高于低表达水平组(85.00%vs 61.40%)(P<0.05)。多因素Cox回归分析显示,TNM分期Ⅲ~Ⅳ期(HR=2.387,95%CI:1.004~5.671)、淋巴结转移(HR=2.667,95%CI:1.021~6.969)、lncRNA TPT1-AS1≥3.405(HR=2.023,95%CI:1.076~3.803)为结肠癌患者预后独立风险因素,miR-30c-5p≥0.306(HR=0.175,95%CI:0.012~0.423)为独立保护因素(P<0.05)。结论结肠癌组织中lncRNA TPT1-AS1表达显著上调,miR-30c-5p表达显著下调,两者与TNM分期、浸润深度、淋巴结转移相关,为患者预后独立影响因素,可能成为结肠癌预后评估的标志物。展开更多
基金Supported by National Natural Science Foundation of China,No.11272342/A0205
文摘AIM:To reveal the functions of micro RNAs(mi RNAs) with respect to hepatic stellate cells(HSCs) in response to portal hypertension.METHODS:Primary rat HSCs were exposed to static water pressure(10 mm Hg,1 h) and the pressureinduced mi RNA expression profile was detected by next-generation sequencing. Quantitative real-time polymerase chain reaction was used to verify the expression of mi RNAs. A potential target of Mi R-9a-5p was measured by a luciferase reporter assay and Western blot. CCK-8 assay and Transwell assay were used to detect the proliferation and migration of HSCs under pressure.RESULTS:According to the profile,the expression of mi R-9a-5p was further confirmed to be significantly increased after pressure overload in HSCs(3.70 ± 0.61 vs 0.97 ± 0.15,P = 0.0226),which resulted in the proliferation,migration and activation of HSCs. In vivo,the up-regulation of mi R-9a-5p(2.09 ± 0.91 vs 4.27 ± 1.74,P = 0.0025) and the down-regulation of Sirt1(2.41 ± 0.51 vs 1.13 ± 0.11,P = 0.0006) were observed in rat fibrotic liver with portal hypertension. Sirt1 was a potential target gene of mi R-9a-5p. Through restoringthe expression of Sirt1 in mi R-9a-5p transfected HSCs on pressure overload,we found that overexpression of Sirt1 could partially abrogate the mi R-9a-5p mediated suppression of the proliferation,migration and activation of HSCs. CONCLUSION:Our results suggest that during liver fibrosis,portal hypertension may induce the proliferation,migration and activation of HSCs through the up-regulation of mi R-9a-5p,which targets Sirt1.
基金National Natural Science Foundation of China(21322705,41121004,21190051,and 21177091)
文摘The mechanism of health effects caused by organohalogen pollutants, e.g., toxins from electronic waste(e-waste), is poorly understood. We supposed that micro RNAs(mi RNAs), an important post-transcriptional regulator, could play a role in this process. In this study, fasting peripheral blood samples were collected from residents living at an e-waste site in northern China and a nearby reference population. Concentrations of e-waste related organohalogen pollutants in plasma from the exposure group were higher than the corresponding measurement in the reference group. Correspondingly, sixty mi RNAs in plasma showed > 2-fold change between the two groups in microarray analysis. Among them, mi R-125a-5p was confirmed to be upregulated by q RT-PCR and its validated targets were enriched in responses to xenobiotics and cancer related pathways. Furthermore, significant positive correlations were found between levels of mi R-125a-5p in plasma and reactive oxygen species(ROS) in polymorphonuclear neutrophil leukocytes(P < 0.05). These evidences suggested oxidative stress might be an intermediate between e-waste related POPs exposure and alteration of plasma mi RNA.
文摘目的探讨结肠癌组织中长链非编码RNA(lncRNA)肿瘤蛋白翻译调节因子1(TPT1)-反义RNA1(AS1)、微小RNA(miR)-30c-5p的表达及与病理特征、预后的关系。方法选取2015年1月至2017年12月深圳大学附属第一医院收治的117例接受根治性或姑息性手术切除结肠癌患者,均行手术切除结肠癌组织及癌旁组织。采用qRT-PCR检测lncRNA TPT1-AS1、miR-30c-5p表达水平,分析lncRNA TPT1-AS1、miR-30c-5p表达水平与结肠癌病理特征的关系,采用Pearson相关性检验分析结肠癌组织中lncRNA TPT1-AS1与miR-30c-5p表达水平的相关性,Kaplan-Meier曲线绘制不同lncRNA TPT1-AS1、miR-30c-5p表达水平结肠癌患者3年累积生存率,Cox回归分析结肠癌患者预后影响因素。结果结肠癌组织中lncRNA TPT1-AS1表达水平明显高于癌旁组织(3.405±0.555 vs 1.766±0.096),miR-30c-5p表达水平(0.306±0.146 vs 0.872±0.267)明显低于癌旁组织(P<0.05)。结肠癌lncRNA TPT1-AS1表达水平TNM分期Ⅲ~Ⅳ期明显高于Ⅰ~Ⅱ期(3.651±0.579 vs 3.257±0.486),浸润深度T_(3)~T_(4)明显高于T_(1)~T_(2)(3.523±0.601 vs 3.301±0.491),有淋巴结转移明显高于无淋巴结转移(3.614±0.585 vs 3.220±0.456),差异均有统计学意义(P<0.05);miR-30c-5p表达水平TNM分期Ⅲ~Ⅳ期明显低于Ⅰ~Ⅱ期(0.251±0.126 vs 0.346±0.145),浸润深度T_(3)~T_(4)明显低于T_(1)~T_(2)(0.270±0.119 vs 0.338±0.162),有淋巴结转移明显低于无淋巴结转移(0.255±0.125 vs 0.351±0.151),差异均有统计学意义(P<0.05)。Pearson相关性分析显示,结肠癌组织中lncRNA TPT1-AS1与miR-30c-5p表达水平呈负相关(r=-0.572,P<0.05)。Kaplan-Meier生存曲线显示,lncRNA TPT1-AS1高表达水平组3年累积生存率明显低于低表达水平组(59.32%vs 87.93%),miR-30c-5p高表达水平组3年累积生存率明显高于低表达水平组(85.00%vs 61.40%)(P<0.05)。多因素Cox回归分析显示,TNM分期Ⅲ~Ⅳ期(HR=2.387,95%CI:1.004~5.671)、淋巴结转移(HR=2.667,95%CI:1.021~6.969)、lncRNA TPT1-AS1≥3.405(HR=2.023,95%CI:1.076~3.803)为结肠癌患者预后独立风险因素,miR-30c-5p≥0.306(HR=0.175,95%CI:0.012~0.423)为独立保护因素(P<0.05)。结论结肠癌组织中lncRNA TPT1-AS1表达显著上调,miR-30c-5p表达显著下调,两者与TNM分期、浸润深度、淋巴结转移相关,为患者预后独立影响因素,可能成为结肠癌预后评估的标志物。
