Cellular microRNAs(miRNAs) have been shown to modulate HCV infection via directly acting on the viral genome or indirectly through targeting the virus-associated host factors. Recently we generated a comprehensive map...Cellular microRNAs(miRNAs) have been shown to modulate HCV infection via directly acting on the viral genome or indirectly through targeting the virus-associated host factors. Recently we generated a comprehensive map of HCV–miRNA interactions through genome-wide miRNA functional screens and transcriptomics analyses. Many previously unappreciated cellular miRNAs were identified to be involved in HCV infection, including miR-135a, a human cancerrelated miRNA. In the present study, we investigated the role of miR-135a in regulating HCV life cycle and showed that it preferentially enhances viral genome replication. Bioinformatics-based integrative analyses and subsequent functional assays revealed three antiviral host factors, including receptor interacting serine/threonine kinase 2(RIPK2), myeloid differentiation primary response 88(MYD88), and C-X-C motif chemokine ligand 12(CXCL12), as bona fide targets of miR-135a. These genes have been shown to inhibit HCV infection at the RNA replication stage. Our data demonstrated that repression of key host restriction factors mediated the proviral effect of miR-135a on HCV propagation. In addition,miR-135a hepatic abundance is upregulated by HCV infection in both cultured hepatocytes and human liver, likely mediating a more favorable environment for viral replication and possibly contributing to HCV-induced liver malignancy.These results provide novel insights into HCV–host interactions and unveil molecular pathways linking miRNA biology to HCV pathogenesis.展开更多
目的 探究多层螺旋CT灌注参数联合血清微小RNA-135b-5p(microRNA-135b-5p,miR-135b-5p)水平检测对肾细胞癌(以下简称肾癌)患者预后的预测价值。方法 选取2020年12月—2023年12月就诊于睢县中医院的65例肾癌患者为研究组,另取同期65名健...目的 探究多层螺旋CT灌注参数联合血清微小RNA-135b-5p(microRNA-135b-5p,miR-135b-5p)水平检测对肾细胞癌(以下简称肾癌)患者预后的预测价值。方法 选取2020年12月—2023年12月就诊于睢县中医院的65例肾癌患者为研究组,另取同期65名健康体检者为对照组。比较研究组和对照组、不同临床病理特征、不同预后肾癌患者多层螺旋CT灌注参数、血清miR-135b-5p水平,分析多层螺旋CT灌注参数、血清miR-135b-5p与临床病理特征的相关性,分析多层螺旋CT灌注参数、血清miR-135b-5p预测预后不良的价值。结果 研究组血流量、通透性、相对血容比低于对照组,血清miR-135b-5p水平高于对照组(t=27.560、26.009、21.957、28.451,均P<0.05);不同临床病理特征患者多层螺旋CT灌注参数(血流量、通透性、相对血容比)、血清miR-135b-5p水平比较:Ⅰ~Ⅱ期患者低于Ⅲ~Ⅳ期患者(t=14.579、13.139、11.307、16.481),低分化患者高于中高分化患者(t=18.382、17.267、14.839、19.105),淋巴结转移患者高于无淋巴结转移患者(t=17.725、15.818、14.169、18.975)(均P<0.05);血流量、通透性、相对血容比、血清miR-135b-5p水平与TNM分期(r=0.614、0.591、0.563、0.639)、淋巴结转移(r=0.652、0.611、0.582、0.673)呈正相关,与分化程度(r=-0.674、-0.623、-0.599、-0.701)呈负相关(均P<0.05);预后不良组血流量、通透性、相对血容比、血清miR-135b-5p水平高于预后良好组(t=16.441、15.011、12.504、16.678,均P<0.05);多层螺旋CT灌注参数、血清miR-135b-5p联合预测肾癌患者预后不良的曲线下面积(area under the curve,AUC)为0.905,高于单一指标预测(Z=1.975、2.171、1.951、2.179,均P<0.05)。结论 联合检测多层螺旋CT灌注参数、血清miR-135b-5p在预测肾癌患者预后不良发生风险方面具有较高预测效能。展开更多
基金supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health
文摘Cellular microRNAs(miRNAs) have been shown to modulate HCV infection via directly acting on the viral genome or indirectly through targeting the virus-associated host factors. Recently we generated a comprehensive map of HCV–miRNA interactions through genome-wide miRNA functional screens and transcriptomics analyses. Many previously unappreciated cellular miRNAs were identified to be involved in HCV infection, including miR-135a, a human cancerrelated miRNA. In the present study, we investigated the role of miR-135a in regulating HCV life cycle and showed that it preferentially enhances viral genome replication. Bioinformatics-based integrative analyses and subsequent functional assays revealed three antiviral host factors, including receptor interacting serine/threonine kinase 2(RIPK2), myeloid differentiation primary response 88(MYD88), and C-X-C motif chemokine ligand 12(CXCL12), as bona fide targets of miR-135a. These genes have been shown to inhibit HCV infection at the RNA replication stage. Our data demonstrated that repression of key host restriction factors mediated the proviral effect of miR-135a on HCV propagation. In addition,miR-135a hepatic abundance is upregulated by HCV infection in both cultured hepatocytes and human liver, likely mediating a more favorable environment for viral replication and possibly contributing to HCV-induced liver malignancy.These results provide novel insights into HCV–host interactions and unveil molecular pathways linking miRNA biology to HCV pathogenesis.
文摘目的 探究多层螺旋CT灌注参数联合血清微小RNA-135b-5p(microRNA-135b-5p,miR-135b-5p)水平检测对肾细胞癌(以下简称肾癌)患者预后的预测价值。方法 选取2020年12月—2023年12月就诊于睢县中医院的65例肾癌患者为研究组,另取同期65名健康体检者为对照组。比较研究组和对照组、不同临床病理特征、不同预后肾癌患者多层螺旋CT灌注参数、血清miR-135b-5p水平,分析多层螺旋CT灌注参数、血清miR-135b-5p与临床病理特征的相关性,分析多层螺旋CT灌注参数、血清miR-135b-5p预测预后不良的价值。结果 研究组血流量、通透性、相对血容比低于对照组,血清miR-135b-5p水平高于对照组(t=27.560、26.009、21.957、28.451,均P<0.05);不同临床病理特征患者多层螺旋CT灌注参数(血流量、通透性、相对血容比)、血清miR-135b-5p水平比较:Ⅰ~Ⅱ期患者低于Ⅲ~Ⅳ期患者(t=14.579、13.139、11.307、16.481),低分化患者高于中高分化患者(t=18.382、17.267、14.839、19.105),淋巴结转移患者高于无淋巴结转移患者(t=17.725、15.818、14.169、18.975)(均P<0.05);血流量、通透性、相对血容比、血清miR-135b-5p水平与TNM分期(r=0.614、0.591、0.563、0.639)、淋巴结转移(r=0.652、0.611、0.582、0.673)呈正相关,与分化程度(r=-0.674、-0.623、-0.599、-0.701)呈负相关(均P<0.05);预后不良组血流量、通透性、相对血容比、血清miR-135b-5p水平高于预后良好组(t=16.441、15.011、12.504、16.678,均P<0.05);多层螺旋CT灌注参数、血清miR-135b-5p联合预测肾癌患者预后不良的曲线下面积(area under the curve,AUC)为0.905,高于单一指标预测(Z=1.975、2.171、1.951、2.179,均P<0.05)。结论 联合检测多层螺旋CT灌注参数、血清miR-135b-5p在预测肾癌患者预后不良发生风险方面具有较高预测效能。
