MicroRNA-34b/c is involved in the response of human liver cells to the Corylus avellana L. hazelnut extract

Abstract Background Epigenetic regulation by microRNAs (miRs) underlies liver tissue biology and affects the hepatocytes response to pathogens, drugs, and food-derived molecules.Methods and results In this study we characterized the epigenetic role driven by an ethanolic extract of hazelnut (Corylus Avellana L, HZN) in both THLE-2 human primary hepatocytes and HepG2 human hepatocarcinoma cells (HCC), in terms of microRNA-34b/c involvement. Both the precursor transcript and mature molecules (miR-34b and miR-34c) were found hyper-expressed in primary cells if compared to HCC (P<0.05). When treated with HZN (0.04-0.4 mg/ml) for 72h, microRNA-34b/c underwent significant stimulation (≥ 2-fold change, P<0.05) exclusively in primary hepatocytes, whereas 144h of continuous HZN treatment were required to induce such an increase in HCC, demonstrating a different kinetics of miR-34 stimulation in liver cells, according to their either cancer or non-cancer phenotype. In THLE-2 cells, miR-34b/c stimulation plays a significant antioxidant role; when challenged with oxygen peroxide (H2O2 1000-2000 µM, 24h), cells are significantly protected from oxidative stress if pre-treated with HZN, the H2O2-driven cytotoxicity and reactive oxygen species generation being recovered by hazelnut. In HCC cells, prolonged exposure (144h) to high HZN concentration (0.4 mg/ml) triggers cell growth arrest and cell death, demonstrating a promising potential anti-neoplastic function of the biomolecules composing the hazelnut extract.Conclusions Overall, our experimental findings demonstrate the epigenomic effect of the Corylus Avellana L. extract in human liver cells in vitro, highlighting the great potential of tree nuts consumption for personalized nutrition and of its bioactive molecules for possible therapeutic options.