A circulating microRNA signature as noninvasive diagnostic and prognostic biomarkers for nonalcoholic steatohepatitis

Abstract

BackgroundNoninvasive biomarkers are urgently needed for patients with nonalcoholic steatohepatitis (NASH) to assist in diagnosis, monitoring disease progression and assessing treatment response. Recently several exploratory studies showed that circulating level of microRNA is associated with NASH and correlated with disease severity. Although these data were encouraging, the application of circulating microRNA as biomarkers for patient screening and stratification need to be further assessed under well-controlled conditions.ResultsThe expression of circulating microRNAs were profiled in diet-induced NASH progression and regression models to assess the diagnostic and prognostic values and the translatability between preclinical mouse model and men. Since these mice had same genetic background and were housed in the same conditions, there were minimal confounding factors. Histopathological lesions were analyzed at distinct disease progression stages along with microRNA measurement which allows longitudinal assessment of microRNA as NASH biomarkers. Next, differentially expressed microRNAs were identified and validated in an independent cohorts of animals. Thirdly, these microRNAs were examined in a NASH regression model to assess whether they would respond to NASH treatment.MicroRNA profiling in two independent cohorts of animals validated the up-regulation of 6 microRNAs (miR-122, miR-192, miR-21, miR-29a, miR-34a and miR-505) in NASH mice, which was designated as the circulating microRNA signature for NASH. The microRNA signature could accurately distinguish NASH mice from lean mice, and it responded to chow diet treatment in a NASH regression model. To further improve the performance of microRNA-based biomarker, a new composite biomarker was proposed, which consists of miR-192, miR-21, miR-505 and ALT. The new composite biomarker outperformed the microRNA signature in predicting NASH mice which had NAS > 3, and deserves further validations in large scale studies.ConclusionThe present study supported the translation of circulating microRNAs between preclinical models and humans in NASH pathogenesis and progression. The microRNA-based composite biomarker may be used for non-invasive diagnosis, clinical monitoring and assessing treatment response for NASH.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4575-3) contains supplementary material, which is available to authorized users.

Progression and Regression of Hepatic Lesions in a Mouse Model of NASH Induced by Dietary Intervention and Its Implications in Pharmacotherapy

“…Although the mechanisms for those dietary components caused hepatic lesions have been intensely studied, lesion regression and reversal have not been systematically studied. Besides the metabolic pathways, recent studies have shown that micro RNAs, such as miR-122, miR-192, miR-21, miR-29a, miR-34a, and miR-505, are up or down regulated at disease state of NASH and may play a role in the disease progression (Liu et al, 2018 ).…”

Circulating MicroRNA-4739 May Be a Potential Biomarker of Critical Limb Ischemia in Patients with Diabetes

“…MicroRNAs (miRNAs) are small (18–22 nucleotides) noncoding RNA molecules that regulate the expression of hundreds of mRNAs at the posttranscriptional level through binding to target mRNA, resulting in either mRNA degradation or translational repression [ 14 , 15 ]. miRNAs are present in extracellular spaces and affect many physiological processes [ 16 ].…”

The Emerging Role of MicroRNAs in NAFLD: Highlight of MicroRNA-29a in Modulating Oxidative Stress, Inflammation, and Beyond

“…Studies from Lambrecht et al as we as Jampoka et al highlighted miR-29a as an essential part in predictive algorithm for NAFLD [29,31]. Furthermore, studies using mouse model also confirmed the close involvement of miR-29a in representing the progression of NAFLD [44,73] and NASH [74,75]. A non-exhaustive list of miR-29a with altered level in liver diseases is provided in Table 3.…”