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

Shun Long Weng, Kai Yao Huang, Julia Tzu Ya Weng, Fang Yu Hung, Tzu Hao Chang, Tzong Yi Lee

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


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 pre-miRNAs. 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 infection and carcinogenesis. These viral miRNAs pose as promising candidates for the development of antiviral drugs. More importantly, the identified subtype-specific miRNAs have the potential to be used as biomarkers for HPV subtype determination.

Original languageEnglish
Pages (from-to)1102-1114
Number of pages13
JournalBriefings in Bioinformatics
Issue number6
Publication statusPublished - May 30 2017


  • Big data analytics
  • HPV
  • Human papillomavirus
  • Viral microRNA-medicated networks
  • Virus encoded microRNA

ASJC Scopus subject areas

  • Information Systems
  • Molecular Biology


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