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Plasma MicroRNAs as sensitive and specific biomarkers of tissue injury
Omar F Laterza1, Lee Lim, Philip W Garrett-Engele
1Merck Research Laboratories, Clinical Development Laboratory, Rahway, NJ, USA.
Background:
MicroRNAs (miRNAs) are endogenous, small noncoding RNAs. Because of their size, abundance, tissue specificity, and relative stability in plasma, miRNAs hold promise as unique accessible biomarkers to monitor tissue injury.
Methods:
We investigated the use of liver-, muscle- and brain-specific miRNAs as circulating biomarkers of tissue injury. We used a highly sensitive quantitative PCR assay to measure specific miRNAs (miR-122, miR-133a, and miR-124) in plasma samples from rats treated with liver or muscle toxicants and from a rat surgical model of stroke.
Results:
We observed increases in plasma concentrations of miR-122, miR-133a, and miR-124 corresponding to injuries in liver, muscle, and brain, respectively. miR-122 and miR-133a illustrated specificity for liver and muscle toxicity, respectively, because they were not detectable in the plasma of animals with toxicity to the other organ. This result contrasted with the results for alanine aminotransferase (ALT) and aspartate aminotransferase, which were both increased with either organ toxicity. Furthermore, miR-122 exhibited a diagnostic sensitivity superior to that of ALT when the results were correlated to the liver histopathologic results. The miR-124 concentration increased in the plasma of rats 8 h after surgery to produce brain injury and peaked at 24 h, while the miR-122 and miR-133a concentrations remained at baseline values.
Conclusions:
These results demonstrate that tissue-specific miRNAs may serve as diagnostically sensitive plasma biomarkers of tissue injury.
Insights
Tissue-specific microRNAs (miRNAs) show promise as sensitive plasma biomarkers for detecting organ injury. Studies confirm that circulating miRNAs like miR-122, miR-133a, and miR-124 accurately indicate liver, muscle, and brain damage, respectively.
Area of Science:
- Biochemistry
- Molecular Biology
- Biomarker Discovery
Background:
- MicroRNAs (miRNAs) are small, noncoding RNAs found in plasma.
- Their stability and tissue specificity make them potential biomarkers for tissue injury.
- Current biomarkers lack specificity and sensitivity for certain injuries.
Purpose of the Study:
- To investigate the utility of liver-, muscle-, and brain-specific miRNAs as circulating biomarkers.
- To assess the diagnostic accuracy of these miRNAs in detecting tissue damage.
- To compare miRNA biomarker performance against traditional markers like ALT.
Main Methods:
- Quantitative PCR was used to measure plasma levels of miR-122, miR-133a, and miR-124.
- Rats were subjected to liver/muscle toxicants or a surgical stroke model.
- Plasma miRNA concentrations were correlated with induced tissue injuries.
Main Results:
- Plasma concentrations of miR-122, miR-133a, and miR-124 increased with liver, muscle, and brain injury, respectively.
- miR-122 and miR-133a demonstrated specificity for liver and muscle toxicity.
- miR-122 showed superior diagnostic sensitivity compared to ALT for liver injury.
- miR-124 levels rose post-stroke, peaking at 24 hours.
Conclusions:
- Tissue-specific miRNAs are diagnostically sensitive plasma biomarkers for tissue injury.
- These miRNAs offer a more specific and sensitive approach to injury detection.
- Circulating miRNAs represent a novel class of biomarkers for clinical diagnostics.
