This study aimed to investigate the functional implications of microRNA-122 (miR-122) in the pathogenesis of NAFLD and the possible molecular mechanisms.
We identified four miRNAs overexpressed in obesity (miR-222, miR-142-3, miR-140-5p, and miR-143) and two miRNAs (miR-122 and miR-34a) overexpressed in children with obesity and nonalcoholic fatty liver disease (NAFLD) and/or insulin resistance.
Circulating miRNAs, especially miR-122, might be promising diagnostic biomarkers for NAFLD with high-accuracy, and more large-sample studies are required to support the above findings in the future.
Both miRNA-122, in distinguishing NAFLD from healthy controls, and miRNA-34a, in distinguishing NASH from NAFL, showed moderate diagnostic accuracy. miRNA-122 was upregulated in every scenario of NAFL, NASH and fibrosis.
Patients with NAFLD are known to have altered levels of miR-122, therefore we suggest that miR-122 mimics could play a useful role in reversing liver steatofibrosis and insulin resistance seen in patients with NAFLD.
Interestingly, receiver operating characteristic (ROC) curve analysis revealed that miR-34a and miR-122 are potential markers for discriminating NAFLD patients from healthy controls with an area under the curve (AUC) values of 0.781 and 0.858, respectively.
We examined the correlation between the circulating levels and hepatic expression of miR122 and miR33a/b*, the key lipid metabolism-related gene expression and the clinicopathological factors of obese women with NAFLD.
Serum miR-122, -192 and -34a levels were correlated with steatosis (R = 0.302, 0.323 and 0.470, respectively, <i>P</i> < 0.05) and inflammatory activity (R = 0.445, 0.447 and 0.517, respectively, <i>P</i> < 0.01); only serum miR-16 levels were associated with fibrosis (R = 0.350, <i>P</i> < 0.05) in patients with NAFLD.
Multivariate analysis identified HCC and/or histological components of NASH as morphological factors that independently influenced serum miR-122 levels at the diagnosis of NAFLD.
miR-122 plays a role of physiological significance in the biology of NAFLD; circulating miRNAs mirror the histological and molecular events occurring in the liver.
Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192--two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver.
Serum levels of miR-34a and miR-122 may represent novel, noninvasive biomarkers of diagnosis and histological disease severity in patients with CHC or NAFLD.