BACKGROUND The liver is frequently subject to insult because of viral infection, alcohol abuse, or toxic chemical exposure. Extensive research has been conducted to identify blood markers that can better discern liver damage, but little progress has been achieved in clinical practice. Recently, circulating microRNAs (miRNAs) have been reported as potential biomarkers for the noninvasive diagnosis of cancer. In this study, we investigated whether plasma miRNAs have diagnostic utility in identifying liver disease. METHODS The study was divided into 2 phases: marker selection by real-time quantitative PCR analysis of a small set of plasma samples, and marker validation with a large set of plasma samples from 83 patients with chronic hepatitis B viral infections, 15 patients with skeletal muscle disease, and 40 healthy controls. Two mouse model systems, d-galactosamine- and alcohol-induced liver injury, were also developed to evaluate whether differences in miRNA concentration were associated with various liver diseases. RESULTS Among the miRNA candidates identified, miR-122 presented a disease severity–dependent change in plasma concentration in the patients and animal models. Compared with an increase in aminotransferase activity in the blood, the change in miR-122 concentration appeared earlier. Furthermore, this change was more specific for liver injury than for other organ damage and was more reliable, because the change was correlated with liver histologic stage. CONCLUSIONS Our findings suggest that circulating miR-122 has potential as a novel, predictive, and reliable blood marker for viral-, alcohol-, and chemical-induced liver injury.

Pre-eclampsia is a leading cause of maternal and foetal morbidity and mortality worldwide. Insufficient uteroplacental oxygenation is believed to be responsible for the disease. However, what molecular events involve in hypoxic responses and how they affect placental development remain unclear. Recently, miRNAs have emerged as a new class of molecules in response to hypoxia. We show here that the expression of microRNA-210 (mir-210) is up-regulated in patients with pre-eclampsia, as well as in trophoblast cells cultured under hypoxic conditions. Ectopic expression of mir-210 inhibited the migration and invasion capability of trophoblast cells. Ephrin-A3 and Homeobox-A9, which related with cell migration and vascular remodelling, were then experimentally validated as the functional targets of mir-210 both in vivo and in vitro. Using luciferase reporter, chromatin immunoprecipitation (ChIP) and small interfering RNA (siRNA) experiments, we finally identified a new transcriptional mechanism that the overexpression of mir-210 under hypoxia was regulated by NF-κB transcriptional factor p50, apart from the well-known HIF 1α. Taken together, our study implicates an important role for mir-210 in the molecular mechanism of pre-eclampsia.

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