Plasma MicroRNAs as Sensitive and Specific Biomarkers of Tissue Injury (original) (raw)

Journal Article

Omar F Laterza ,

Merck Research Laboratories

, Clinical Development Laboratory, Rahway, NJ

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Lee Lim ,

Sirna Therapeutics

, San Francisco, CA

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Philip W Garrett-Engele ,

Merck Research Laboratories

, Molecular Profiling and Research Informatics, Boston, MA; Merck Research Laboratories

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Katerina Vlasakova ,

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Nagaraja Muniappa ,

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Wesley K Tanaka ,

Merck Research Laboratories

, Clinical Development Laboratory, Rahway, NJ

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Jason M Johnson ,

Merck Research Laboratories

, Molecular Profiling and Research Informatics, Boston, MA; Merck Research Laboratories

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Joseph F Sina ,

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Thomas L Fare ,

External Scientific Affairs

, West Point, PA

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Frank D Sistare ,

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... Show more

Published:

01 November 2009

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Omar F Laterza, Lee Lim, Philip W Garrett-Engele, Katerina Vlasakova, Nagaraja Muniappa, Wesley K Tanaka, Jason M Johnson, Joseph F Sina, Thomas L Fare, Frank D Sistare, Warren E Glaab, Plasma MicroRNAs as Sensitive and Specific Biomarkers of Tissue Injury, Clinical Chemistry, Volume 55, Issue 11, 1 November 2009, Pages 1977–1983, https://doi.org/10.1373/clinchem.2009.131797
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Abstract

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.

© 2009 The American Association for Clinical Chemistry

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