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Updated: Feb 13, 2026

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

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Suppression of MicroRNA 424 Levels by Human Papillomaviruses Is Necessary for Differentiation-Dependent Genome

Shiyuan Hong1, Shouqiang Cheng1, William Songock2

  • 1Department of Microbiology-Immunology, Northwestern University, Feinberg, School of Medicine, Chicago, Illinois, USA.

Journal of Virology
|October 6, 2017
PubMed

Insights

High-risk human papillomaviruses (HPVs) suppress miR-424, a microRNA crucial for regulating viral replication. This suppression impacts DNA damage repair pathways, aiding HPV

Area of Science:

  • Virology
  • Molecular Biology
  • Cancer Research

Background:

  • High-risk human papillomaviruses (HPVs) depend on epithelial differentiation and DNA damage pathways for replication.
  • HPVs manipulate cellular transcription factors and microRNAs (miRNAs) to regulate viral activities.
  • miR-424 is a known repressed miRNA in HPV-positive cervical and oropharyngeal cancers.

Purpose of the Study:

  • To investigate the role of miR-424 in the replication of high-risk HPVs.
  • To elucidate the mechanism by which HPV affects miR-424 levels and its downstream targets.
  • To establish miR-424 as a regulatory factor in the HPV life cycle.

Main Methods:

  • Analyzing miR-424 levels in HPV-positive cell lines with episomal and integrated HPV genomes.
  • Introducing miR-424 expression vectors to assess its impact on HPV genome levels.
  • Quantifying levels of putative miR-424 targets, CHK1 and Wee1, in HPV-positive cells.

Main Results:

  • miR-424 levels were suppressed in cell lines maintaining HPV 31 or 16 episomes and integrated HPV genomes.
  • Restoring miR-424 expression reduced HPV genome levels in undifferentiated cells and viral amplification during differentiation.
  • Levels of CHK1 and Wee1, key DNA damage repair proteins targeted by miR-424, were suppressed in HPV-positive cells.

Conclusions:

  • miR-424 plays a critical role in regulating HPV replication.
  • HPV E6 and E7 oncoproteins suppress miR-424 levels, which is essential for controlling CHK1 levels.
  • Targeting miR-424 by HPV is a key strategy for modulating DNA damage repair pathways and facilitating viral replication.
Keywords:
CHK1DNA damage repairHPVamplificationcheck pointmicroRNA

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