The role of microRNAs in human liver cancers

Abstract

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver of global importance. Recent studies of the expression and role of microRNA (miRNA) in HCC are providing new insights into disease pathogenesis. In addition, therapeutic efforts targeting specific miRNAs are being evaluated in animal models of HCC. The potential of miRNAs as biomarkers of disease or prognostic markers is being explored. Herein, we review studies of miRNA expression in human HCC, and discuss recent advances in knowledge about the involvement and role of selected miRNAs in disease pathogenesis, as biomarkers, or as therapeutic targets for HCC.

Figure 1

Several miRNAs act synergistically to promote HCC through the modulation of multiple cell phenotypes.

Figure 2

The inflammatory cytokine Interleukin 6 (IL-6) plays an important role in hepatocarcinogenesis through the modulation of STAT3 pathway, MAPK route and cell cycle progression. Growing evidence suggests a role for miRNAs in the regulation of IL-6. miR-26 was shown to be inversely related to IL-6 expression in a cohort of Chinese HBV-related HCC where low expression of miR-26 correlated with dismal outcome. Liver expression of miR-26 is higher in women than men. Consistently, estrogen-dependent IL-6 over-expression in female rats was shown to be responsible for the lower incidence of HCC in female. The oncogenic miR-21 was shown to be induced by IL-6 in a STAT-3-dependent mechanism, suggesting an auto-stimulatoruy loop.