Reanalysis of microRNA expression profiles identifies novel biomarkers for hepatocellular carcinoma prognosis.

The aim of our study is to identify microRNAs (miRNAs) that have significance in the prognosis and pathogenesis of hepatocellular carcinoma (HCC). The miRNAs differentially expressed in HCC were examined by using a human miRNA microarray dataset, and then the acquired candidates were screened by another microarray dataset. As a result, we got 25 miRNAs which were aberrantly expressed in cancer and meanwhile predicated distinct prognosis. Among them, miR-139-5p was down-regulated in HCC and its low expression in cancer tissue meant poor prognosis. Additionally, we demonstrated that its low expression was also related to several clinicopathologic characteristics such as vein invasion, BCLC stage, p-AKT expression, and pIGFR1 expression. In vitro, it has been discovered that treatment of HCC cells with a miR-139-5p mimic lead to inhibition of cell growth and migration. Moreover, luciferase assay showed that KPNA4 was not the direct target of miR-139-5p. Ectopic expression of miR-139-5p has not repressed the expression of KPNA4, but inhibited the nuclear import of NF-κB and phosphorylation of Akt. In conclusion, for the first time, we identify 25 deregulated miRNAs that are associated with prognosis and prove that miR-139-5p functions as a tumor suppressor in HCC and its low expression predicts poor prognosis.