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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Glucocorticoids regulate the human non-coding genome.

Thai Tran1, Robert Kwiat1, Qilin Cao1

  • 1Functional Immunogenomics Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. Bethesda, MD 20892. U.S.A.

Biorxiv : the Preprint Server for Biology
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Glucocorticoids (GCs) significantly alter non-coding RNA expression, with most long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) showing cell-type-specific responses. This study reveals novel GC-regulated non-coding transcripts with potential clinical relevance.

Keywords:
CorticosteroidsGlucocorticoidsHumanLong Noncoding RNAMicroRNARNA sequencingSmall RNASteroidsmiRNA

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Area of Science:

  • Genomics
  • Molecular Biology
  • Pharmacology

Background:

  • Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressive drugs.
  • GCs profoundly impact gene expression, but their effects on non-coding RNAs are largely unknown.
  • Understanding non-coding RNA regulation by GCs is crucial for explaining therapeutic variability.

Purpose of the Study:

  • To comprehensively analyze glucocorticoid regulation of the non-coding genome.
  • To investigate cell type-specific responses of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) to GCs.
  • To identify novel non-coding transcripts modulated by GCs.

Main Methods:

  • Systematic transcriptomic profiling (total RNA-seq and small RNA-seq) of nine human primary cell types.
  • In vitro treatment with GCs followed by RNA sequencing at 2 and 6 hours.
  • Bioinformatic analysis to identify GC-responsive non-coding transcripts.

Main Results:

  • Over 2,000 GC-responsive non-coding transcripts identified, including 654 annotated lncRNAs and 1,376 novel lncRNAs.
  • Non-coding RNA response to GCs was highly cell type-dependent, with 80% of lncRNAs and 97% of miRNAs unique to single cell types.
  • Dozens of facultative lncRNAs were induced de novo by GCs; miRNA regulation appeared independent of their host lncRNAs.

Conclusions:

  • GCs induce widespread, cell type-specific changes in non-coding RNA expression.
  • Identified non-coding RNAs may serve as biomarkers for GC exposure, sensitivity, or resistance.
  • This work provides a framework for understanding non-coding RNA roles in GC response heterogeneity.