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A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
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A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions

Published on: July 18, 2013

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Dysregulation of host cellular genes targeted by human papillomavirus (HPV) integration contributes to HPV-related

Ruiyang Zhang1, Congle Shen1, Lijun Zhao2

  • 1Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.

International Journal of Cancer
|September 30, 2015
PubMed

Insights

Human papillomavirus (HPV) DNA integration into the human genome targets specific genes, potentially driving cervical cancer. This study analyzed 499 integration sites, revealing HPV prefers gene-rich areas and affects nearby gene activity, implicating these integration-targeted genes in carcinogenesis.

Area of Science:

  • Oncology
  • Virology
  • Genetics

Background:

  • Human papillomavirus (HPV) integration into the host genome is a proposed mechanism in cervical carcinogenesis.
  • Integration-targeted cellular genes (ITGs) may play a role in this process.

Purpose of the Study:

  • To comprehensively analyze HPV integration events and their impact on host genes.
  • To investigate the etiological role of ITGs in cervical carcinogenesis.

Main Methods:

  • Meta-analysis of 14 publications, including 499 HPV integration loci.
  • Genomic and bioinformatic analyses (gene ontology, KEGG pathway analysis).
  • Experimental validation of ITG expression and function in cervical cancer cells.

Main Results:

  • HPV DNA preferentially integrates into intragenic and gene-dense chromosomal regions.
  • Genes near integration sites show increased transcriptional activity.
  • Identified ITGs are enriched in tumor-related pathways; MPPED2 and MYC expression are affected by HPV integration.

Conclusions:

  • Dysregulation of ITGs due to HPV integration is implicated in cervical carcinogenesis.
  • Integrated HPV fragments can influence distant gene expression (e.g., MYC) via chromatin interactions.
  • This provides evidence for the etiological involvement of ITGs in cervical cancer development.
Keywords:
HPVMPPED2MYCcervical cancerfunctional annotation analysisintegration

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