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Genome-wide discovery of viral microRNAs based on phylogenetic analysis and structural evolution of various human papillomavirus subtypes

机译:基于系统乳头瘤病毒亚型的系统发育分析和结构演变的基因组 - 病毒微大研讨会

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In mammals, microRNAs (miRNAs) play key roles in controlling posttranscriptional regulation through binding to the mRNAs of target genes. Recently, it was discovered that viral miRNAs may be involved in human cancers and diseases. It is likely that viral miRNAs help viruses enter the latent phase of their life cycle and become undetected by the host’s immune system, while increasing the host’s risk for cancer development. Cervical cancer is typically related to the infection of human papillomavirus (HPV) through sexual transmission. To further understand the molecular mechanisms underlying the associations of HPV infection with genital diseases, we developed a systematic method for viral miRNA identification and viral miRNA-mediated regulatory network construction based on genome-wide sequence analysis. The complete genomes of certain high-risk HPV subtypes were used to predict putative viral pre-miRNAs by bioinformatics approaches. In addition, small RNA libraries in human cervical lesions from existing publications were collected to validate the predicted HPV premiRNAs. For the construction of virally encoded miRNA-mediated regulatory network of HPV infection, cervical squamous epithelial carcinoma gene expression data were extracted from the RNA sequencing platform in The Cancer Genome Atlas; the differentially expressed genes were used to identify the putative targets of viral miRNAs. Predicted cellular target genes of HPV-encoded miRNAs provide an overview of these viral miRNA’s putative functions. Finally, a large-scale genome analysis was carried out to examine the phylogenetic relationship and structural evolution among genital HPV types that have the potential to cause genital cancer. In this study, we discovered putative HPV-encoded miRNAs, which were validated against the small RNA libraries in human cervical lesions. Furthermore, as indicated by their biological functions, host genes targeted by HPV-encoded miRNAs may play significant roles in virus i
机译:在哺乳动物中,MicroRNA(miRNA)通过与靶基因的MRNAs结合来控制治疗后调节的关键作用。最近,发现病毒MiRNA可以参与人类癌症和疾病。病毒miRNA可能有助于病毒进入其生命周期的潜在阶段,并由宿主的免疫系统未被发现,同时增加宿主的癌症发展风险。宫颈癌通常通过性传播感染人乳头瘤病毒(HPV)。为了进一步了解HPV感染与生殖器疾病相关的分子机制,我们开发了一种基于基因组序列分析的病毒MiRNA鉴定和病毒MiRNA介导的调节网络施工的系统方法。某些高风险HPV亚型的完整基因组用于通过生物信息学方法预测推定的病毒前miRNA。此外,收集来自现有出版物的人宫颈病变中的小RNA文库,以验证预测的HPV Premirnas。为了构建病毒编码的MiRNA介导的HPV感染调节网络,从癌症基因组地图集中的RNA测序平台提取宫颈鳞状上皮癌基因表达数据;差异表达的基因用于鉴定病毒miRNA的推定靶标。 HPV编码的miRNA的预测细胞靶基因提供了这些病毒MiRNA推定功能的概述。最后,进行了大规模的基因组分析,以检查生殖器发育关系和具有引起生殖器癌的潜力的生殖器学HPV类型中的结构演变。在这项研究中,我们发现了预算的HPV编码的miRNA,其针对人宫颈病变中的小RNA文库进行了验证。此外,如通过它们的生物学功能所示,通过HPV编码的miRNA靶向的宿主基因可能在病毒I中发挥重要作用

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