Dataset Information

Circulating microRNA-122 as Potential Biomarker for Detection of Testosterone Abuse.

ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and thus influence many cellular and physiological processes. miRNAs are also present in cell-free body fluids such as plasma or serum, and these circulating miRNAs are very stable, sensitive, and specific biomarkers of pathophysiological states. In this study, we investigated whether circulating miRNAs could serve as biomarkers of exogenous testosterone administration. Misuse of testosterone as a performance-enhancing drug is thought to be widespread in sports. Detection of testosterone through the urinary steroid profile of the Athlete Biological Passport faces several obstacles, indicating that new biomarkers are required. To this end, we analyzed plasma miRNA levels by high-throughput quantitative real-time PCR. Plasma samples were obtained before and at several time points after transdermal and oral testosterone administration. Screening identified three potential candidate miRNAs that were altered by both routes of testosterone administration. Longitudinal monitoring of these candidates revealed that variation in two of them (miR-150 and miR-342), relative to the corresponding levels in control samples, was testosterone-independent. However, levels of the liver-specific miR-122 increased 3.5-fold 1 day after drug intake. Given that testosterone is metabolized by the liver, this observation suggests that miR-122 in cell-free fluids may be used as a sensitive biomarker of testosterone misuse via multiple dosing routes and could therefore be integrated into a blood-based multiparametric follow-up.

SUBMITTER: Salamin O

PROVIDER: S-EPMC4865044 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Circulating microRNA-122 as Potential Biomarker for Detection of Testosterone Abuse.

Salamin Olivier O Jaggi Laetitia L Baume Norbert N Robinson Neil N Saugy Martial M Leuenberger Nicolas N

PloS one 20160512 5

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and thus influence many cellular and physiological processes. miRNAs are also present in cell-free body fluids such as plasma or serum, and these circulating miRNAs are very stable, sensitive, and specific biomarkers of pathophysiological states. In this study, we investigated whether circulating miRNAs could serve as biomarkers of exogenous testosterone administration. Misuse of testosterone as a performance-enhancing dr ...[more]

PMID: 27171140

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Project description:Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease that progressively debilitates neuronal cells that control voluntary muscle activity. Biomarkers are urgently needed to facilitate ALS diagnosis and prognosis, and as indicators of therapeutic response in clinical trials. microRNAs (miRNAs), small posttranscriptional modifiers of gene expression, are frequently altered in disease conditions. Besides their important regulatory role in variety of biological processes, miRNAs can also be released into the circulation by pathologically affected tissues and display remarkable stability in body fluids. In a mouse model of ALS that expresses mutated human superoxide dismutase 1 (SOD1-G93A) skeletal muscle is one of the tissues affected early by mutant SOD1 toxicity. To find biomarkers for ALS, we studied miRNA alterations from skeletal muscle and plasma of SOD1-G93A mice, and subsequently tested the levels of the affected miRNAs in the serum from human ALS patients. Fast-twitch and slow-twitch muscles from symptomatic SOD1-G93A mice (age 90 days) and their control littermates were first studied using miRNA microarrays and then evaluated with quantitative PCR from five age groups from neonatal to the terminal disease stage (10-120 days). Among those miRNA changed in various age/gender/muscle groups (miR-206, -1, -133a, -133b, -145, -21, -24), miR-206 was the only one consistently altered during the course of the disease pathology. In both sexes, mature miR-206 was increased in fast-twitch muscles preferably affected in the SOD1-G93A model, with highest expression towards the most severely affected animals. Importantly, miR-206 was also increased in the circulation of symptomatic animals and in a group of 12 definite ALS patients tested. We conclude that miR-206 is elevated in the circulation of symptomatic SOD1-G93A mice and possibly in human ALS patients. Although larger scale studies on ALS patients are warranted, miR-206 is a promising candidate biomarker for this motor neuron disease.

Project description:BackgroundSepsis is now operationally defined as life-threatening organ dysfunction caused by an infection, identified by an acute change in SOFA-Score of at least two points, including clinical chemistry such as creatinine or bilirubin concentrations. However, little knowledge exists about organ-specific microRNAs as potentially new biomarkers. Accordingly, we tested the hypotheses that micro-RNA-122, the foremost liver-related micro-RNA (miR), 1) discriminates between sepsis and infection, 2) is an early predictor for mortality, and 3) improves the prognostic value of the SOFA-score.MethodsWe analyzed 108 patients with sepsis (infection + increase SOFA-Score ≥2) within the first 24h of ICU admission and as controls 20 patients with infections without sepsis (infection + SOFA-Score ≤1). Total circulating miR was isolated from serum and relative miR-122 expression was measured (using spiked-in cel-miR-54) and associated with 30-day survival.Results30-day survival of the sepsis patients was 63%. miR-122 expression was 40-fold higher in non-survivors (p = 0.001) and increased almost 6-fold in survivors (p = 0.013) compared to controls. miR-122 serum-expression discriminated both between sepsis vs. infection (AUC 0.760, sensitivity 58.3%, specificity 95%) and survivors vs. non-survivors (AUC 0.728, sensitivity 42.5%, specificity 94%). Multivariate Cox-regression analysis revealed miR-122 (HR 4.3; 95%-CI 2.0-8.9, p<0.001) as independent prognostic factor for 30-day mortality. Furthermore, the predictive value for 30-day mortality of the SOFA-Score (AUC 0.668) was improved by adding miR-122 (AUC 0.743; net reclassification improvement 0.37, p<0.001; integrated discrimination improvement 0.07, p = 0.007).ConclusionsIncreased miR-122 serum concentration supports the discrimination between infection and sepsis, is an early and independent risk factor for 30-day mortality, and improves the prognostic value of the SOFA-Score, suggesting a potential role for miR-122 in sepsis-related prediction models.

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Circulating microRNA-122 as Potential Biomarker for Detection of Testosterone Abuse.

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Circulating microRNA-122 as Potential Biomarker for Detection of Testosterone Abuse.

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