Combined seven miRNAs for early hepatocellular carcinoma detection with chronic low-dose exposure to microcystin-LR in mice.

Aberrant miRNA expression has been detected in various tumor tissues, which may be considered as a marker for early cancer diagnosis. One miRNA has multiple downstream target genes, which can be regulated by multiple upstream other miRNAs. Hence, this dynamic regulation is likely characterized by volatility, and thus, finding the appropriate time point for tests becomes essential for the use of miRNAs as an early marker of tumor diagnosis. In this study, we established a chronic liver cancer progression model in mice by using low doses of the harmful substance microcystin-LR (MC-LR). On the basis of miRNAs microarray assay, we further tested seven miRNAs that showed characteristic expression changes in pre-hepatocarcinogenesis. Our results showed that the levels of four miRNAs (miR-122-5p, miR-125-5p, miR-199a-5p, and miR-503-5p) decreased dramatically, whereas those of two miRNAs (miR-222-5p and miR-590-5p) increased significantly in the early stages, which were all accompanied by an increase in atypia of hepatocytes. MiR-490-5p was a sensitive molecular, suitable only for evaluation of pathological changes in young mice. Therefore the combination the seven of miRNAs for a set may prove to be an effective method in healthy assessment of environmental toxicants for detection of hepatocarcinogenesis caused by hazardous materials.