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Updated: Jun 17, 2025

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
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Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation

Published on: September 20, 2017

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Dissecting transposable elements and endogenous retroviruses upregulation by HDAC inhibitors in leiomyosarcoma cells:

Nicolò Gualandi1, Martina Minisini1, Alessio Bertozzo1

  • 1Department of Medicine, Università degli Studi di Udine, P.le Kolbe 4, 33100 Udine, Italy.

Genomics
|August 5, 2024
PubMed

Insights

Histone deacetylase inhibitors (HDACIs) upregulate endogenous retroviruses (ERVs) in leiomyosarcoma cells, but surprisingly do not activate the interferon response. Increased A-to-I editing of ERV1 may impact dsRNA stability, suggesting combined HDACI and ADAR inhibition for cancer therapy.

Area of Science:

  • Cancer Biology
  • Immunotherapy
  • Epigenetics

Background:

  • Transposable elements (TEs), including endogenous retroviruses (ERVs), are investigated for their immunomodulatory potential in cancer therapies.
  • TEs can form double-stranded RNAs (dsRNAs) that activate the interferon response, a key component of innate immunity.
  • Histone deacetylase inhibitors (HDACIs) are explored for their ability to modulate gene expression, including TEs, in cancer cells.

Purpose of the Study:

  • To investigate the effects of different HDAC inhibitors (HDACIs) on TE expression in leiomyosarcoma cells.
  • To understand the impact of HDACI-induced TE modulation on the interferon response and potential therapeutic strategies.

Main Methods:

  • Treatment of leiomyosarcoma cells with various HDAC inhibitors targeting HDAC1/2/3.
  • Analysis of endogenous retrovirus (ERV) expression levels.
  • Assessment of interferon response activation.
  • Evaluation of A-to-I editing in ERV1 elements.
  • Measurement of H3K27ac levels and analysis of associated gene expression, including proapoptotic genes like TNFRSF10B.

Main Results:

  • HDAC1/2/3-specific inhibitors upregulated ERVs, particularly ERV1 elements, in leiomyosarcoma cells.
  • Contrary to expectations, the interferon response was not activated upon HDACI treatment.
  • An increase in A-to-I editing of upregulated ERV1 was observed, potentially affecting dsRNA stability.
  • H3K27ac levels increased in LTR12 subfamilies, suggesting a role in regulating proapoptotic gene expression (e.g., TNFRSF10B).

Conclusions:

  • HDACIs modulate TE expression in leiomyosarcoma cells, with specific upregulation of ERVs.
  • A-to-I editing of ERVs may represent a mechanism to dampen the interferon response, despite TE upregulation.
  • Combining HDACIs with ADAR inhibitors could be a viable strategy to induce cancer cell death and enhance immunotherapy.
Keywords:
ADARERVsHDACImmunotherapyInterferonLeiomyosarcomaTNFRSF10B

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