Acute endothelial stresses identify microRNA let-7b-5p and non-coding SLC11A2 (NRAMP2/DMT1) exon as biomarkers that overlap with those detected in malignant and non-malignant diseases
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View abstract on PubMed
Summary
This summary is machine-generated.Acute cellular stress responses, like those from iron or protein translation inhibition, yield biomarkers that overlap with disease states. This suggests early cellular changes may predict future health conditions.
Area Of Science
- Cellular biology
- Molecular biology
- Biomarker discovery
Background
- Disease biomarkers are often identified late, hindering mechanistic understanding and prevention.
- Aberrant cellular responses to common stresses may precede disease states.
Purpose Of The Study
- Model two acute cellular stresses: integrated stress response and iron variation.
- Cross-reference identified cellular changes with known disease biomarkers.
Main Methods
- Human endothelial cells (ECs) treated with cycloheximide or ferric citrate.
- Whole transcriptome RNA-sequencing (RNA-seq) to identify gene and micro(mi)RNA expression changes.
- Novel scripts analyzed exon expression; validations performed using qRT-PCR and RNA-seq on various cell types and plasma.
Main Results
- Ferric citrate caused transient microRNA (miRNA) falls, specifically in let-7 pre-miRNAs, with subsequent increased expression of let-7 target mRNAs.
- Cycloheximide treatment stabilized a novel exon (exon 3B of SLC11A2).
- Validated findings in endothelial cells, PBMCs, and plasma, showing significant let-7 precursor falls after iron exposure.
Conclusions
- Biomarkers associated with normal, acute cellular stress responses show overlap with disease-state biomarkers.
- Further investigation is warranted to explore the predictive potential of these cellular response biomarkers.
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