Progressive miRNA expression profiles in cervical carcinogenesis and identification of HPV-related target genes for miR-29

J Pathol. 2011 Aug;224(4):484-95. doi: 10.1002/path.2873. Epub 2011 Apr 18.


miRNAs have the potential to act on diverse downstream genes, and miRNA signatures of HPV-infected tissues may provide insight into HPV-related carcinogenesis. We set out to profile miRNA expression in HPV-infected samples and relate this to histological and grade-specific alterations in the spectrum of cervical carcinogenesis in vivo. A total of 31 miRNAs showed significant and continuous expression along with the progression from normal cervical tissue to cancer, and six of them were validated in 133 samples. By bioinformatics analyses, we established a putative HPV-associated miRNA-mRNA regulatory network, showing that miR-29 is the most highly enriched. We also found that YY1 and CDK6 were both positively correlated with E6/E7 RNA expression and targeted by tumour-suppressive miR-29. Evidence of miR-29 involvement in HPV infection was further verified in patient samples and by various experimental approaches. Taken together, our results suggest that HPVs have oncogenic properties at least in part by reshaping the milieu of cellular miRNAs. miR-29 restrains cell cycle progression and induces apoptosis via YY1 and CDK6 promoting malignant transformation induced by HPV, although the abnormality of miR-29 in HPV-infected cells might be regulated in an indirect way.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Computational Biology / methods
  • Cyclin-Dependent Kinase 6 / metabolism
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Regulatory Networks / genetics
  • Gene Targeting
  • Human papillomavirus 16 / isolation & purification
  • Humans
  • MicroRNAs / genetics
  • Neoplasm Proteins / metabolism
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / genetics
  • RNA, Neoplasm / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / virology
  • YY1 Transcription Factor / metabolism


  • MIRN29a microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • YY1 Transcription Factor
  • YY1 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6