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Tetraarsenic oxide affects non-coding RNA transcriptome through deregulating polycomb complexes in MCF7 cells.

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Advances in Biological Regulation
|May 1, 2021
PubMed
Summary

Tetraarsenic oxide (TAO) alters non-coding RNA (ncRNA) gene expression in breast cancer cells. TAO acts as an epigenetic regulator by modulating Polycomb Repressive Complex 2 (PRC2) activity.

Keywords:
Gene expressionH3K27me3Non-coding RNAPolycomb complexesTetraarsenic oxide

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Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cancer Research

Background:

  • Non-coding RNAs (ncRNAs) are crucial in cell biology and disease, but their gene expression mechanisms are poorly understood.
  • Understanding ncRNA regulation is vital for developing novel cancer therapies.

Purpose of the Study:

  • To investigate the impact of tetraarsenic oxide (TAO) on ncRNA gene expression in MCF7 breast cancer cells.
  • To elucidate the role of Polycomb Repressive Complexes (PRCs) in TAO-mediated ncRNA regulation.

Main Methods:

  • Genomic analyses to identify TAO-regulated ncRNA genes.
  • Real-time quantitative polymerase chain reaction (RT-qPCR) for validation.
  • Analysis of PRC subunit enrichment and expression changes.
  • Assessment of EZH2 and H3K27me3 levels.
  • Inhibition of EZH2 catalytic activity using GSK343.

Main Results:

  • TAO significantly altered genome-wide ncRNA gene expression in MCF7 cells.
  • TAO-regulated ncRNAs included genes interacting with Polycomb Repressive Complexes (PRCs).
  • TAO decreased EZH2 and H3K27me3 levels, suggesting epigenetic modulation.
  • Inhibition of EZH2 activity mimicked TAO's effect on ncRNA gene expression.

Conclusions:

  • ncRNA gene expression is partly regulated by PRC2.
  • TAO functions as an epigenetic regulator, modulating ncRNA expression via PRCs in breast cancer cells.