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MiR-875 and miR-3144 switch the human papillomavirus 16 E6/E6* mRNA ratio through the EGFR pathway and a direct

Yanyun Li1, Qingqing Cai2, Lin Lin1

  • 1Obstetrics and Gynaecology Hospital, Fudan University, Shanghai 200011, China.

Gene
|September 12, 2018
PubMed

Insights

Two human microRNAs, miR-875 and miR-3144, regulate human papillomavirus (HPV) splicing and oncoprotein expression. These findings reveal a tumor-suppressing role for these specific microRNAs.

Area of Science:

  • Molecular Biology
  • Virology
  • Genetics

Background:

  • Previous studies identified miR-875 and miR-3144 targeting conserved sites in high-risk human papillomaviruses (HR-HPVs).
  • These microRNAs are specific to vertebrates and Homo sapiens, with conserved binding sites in EGFR within Boreoeutheria.

Purpose of the Study:

  • To investigate the role of miR-875 and miR-3144 in regulating HPV16 splicing and oncoprotein expression.
  • To elucidate the mechanism by which these microRNAs influence HPV16 E6/E7 transcripts and related pathways.

Main Methods:

  • Bioinformatics scanning and luciferase reporter assays.
  • Experiments using HPV16+ SiHa cells to assess miRNA effects on viral transcripts and protein levels.
  • EGFR depletion experiments to confirm its role in the miRNA-mediated pathway.

Main Results:

  • miR-875 and miR-3144 target the 5' alternative splice site of HPV16 E6E7 transcripts.
  • These miRNAs reduce unspliced E6 abundance, promote E6* spliced transcripts, and decrease E6/E7 oncoproteins and EGFR expression.
  • EGFR pathway and direct targeting by miRNAs modulate the E6/E6* ratio, suggesting a tumor-suppressing mechanism.

Conclusions:

  • Human miRNAs, specifically miR-875 and miR-3144, can regulate HPV splice isoforms.
  • These miRNAs exert a tumor-suppressing effect by influencing HPV oncoprotein expression and related cellular pathways.
  • The findings highlight an evolutionarily conserved mechanism of miRNA-mediated viral control.
Keywords:
E6 spliced transcriptsEpidermal growth factor receptorEvolutionHuman papillomavirusMicroRNA

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