miR-34a and its novel target, NLRC5, are associated with HPV16 persistence

Infect Genet Evol. 2016 Oct:44:293-299. doi: 10.1016/j.meegid.2016.07.013. Epub 2016 Jul 14.

Abstract

Persistent infection with human papillomavirus (HPV), particularly type 16, is causally associated with cervical cancer and its precursors. The role of miRNAs in HPV16 persistence currently remains unclear. Preliminary analysis of miRNA profile demonstrated that HPV16 infection caused a striking downregulation of miR-34a. Through bioinformatics analysis and dual-luciferase assay with site-directed mutagenesis strategy, NLRC5, a negative regulator of NF-κB signaling, was identified to be a novel interactor of miR-34a. Transfection of miR-34a mimic strikingly downregulated NLRC5 in the HPV16-positive cervical cells, which might result in the nuclear accumulation of NF-κB p65. However, transfection of miR-34a inhibitor exhibited an opposite effect. The antagonistic expressions of NLRC5 and miR-34a were also observed in keratinocytes harboring HPV16 genome as well as in human cervical samples with persistent infection of HPV16. Our data uncover a previously unknown connection among HPV16 persistence, miR-34a and its interactor NLRC5.

Keywords: Cervical cancer; Human papillomavirus type 16, persistent infection; NLRC5; miR-34a; p65.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line
  • Cervix Uteri / virology
  • Female
  • Gene Expression Regulation
  • Human papillomavirus 16* / genetics
  • Human papillomavirus 16* / pathogenicity
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • MicroRNAs / genetics*
  • Middle Aged
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / virology

Substances

  • Intracellular Signaling Peptides and Proteins
  • MIRN34 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • NLRC5 protein, human