A transcriptomic landscape of human papillomavirus 16 E6-regulated gene expression and splicing events

FEBS Lett. 2016 Dec;590(24):4594-4605. doi: 10.1002/1873-3468.12486. Epub 2016 Nov 23.

Abstract

The oncoprotein E6 of high-risk human papillomavirus (HPV) is responsible for the initiation and progression of cervical cancer. In the present study, we performed RNA-sequencing analysis in HPV16 E6-expressing 293T cells and identified 56 differentially expressed genes (DEGs) and a number of cellular pathways significantly affected. We confirmed nine of these DEGs in both cell models and clinical tissue samples. Furthermore, we performed de novo transcriptome assembly of 1128 novel human transcripts and identified 22 that are differentially expressed in the presence of HPV16 E6. In addition, our analysis revealed distinct alternative splicing events in response to HPV16 E6 expression. Overall, the present study provides a comprehensive portrait of transcriptional and splicing signatures, as well as previously unknown genes differentially expressed in response to HPV16 E6, which prompts the need for a complete annotation of the HPV16 E6-regulated transcriptome.

Keywords: HPV16 E6; alternative splicing events; gene expression; transcriptome.

Publication types

  • Letter

MeSH terms

  • Alternative Splicing*
  • Case-Control Studies
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • HEK293 Cells
  • High-Throughput Nucleotide Sequencing
  • Host-Pathogen Interactions
  • Human papillomavirus 16 / genetics*
  • Human papillomavirus 16 / metabolism
  • Humans
  • Oncogene Proteins, Viral / genetics*
  • Oncogene Proteins, Viral / metabolism
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Protein Interaction Mapping
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Transcriptome*
  • Transfection
  • Transgenes
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Repressor Proteins