Abstract
Background: Epigenetic gene regulation is important in human cancer.
Aim of Study: We investigated the possible role of acetyla-tion level in the regulation of microRNAs (miRNAs) expres-sion in hepatocellular carcinoma.
Material and Methods: We first determined the inhibitory concentration (IC20, IC35 and IC50) of the histone deacetylase inhibitor Sodium Butyrate (SB) in HepG2 and Huh7 cells. Then, we analyzed the expression level of five miRNAs (miR-133b, miR-122-5p, miR-26a-5p, miR-539-5p and miR-518f-3p after treatment using qRT-PCR assay. MiRTarBase, MiROB and GeneCards databases were used for the identification of strong validated targets of examined microRNAs, and the detection of possible functions of the selected targets and related pathways.
Results: SB revealed an anti-proliferative effect in both HepG2 and Huh7 cells, with IC50 values of 6.7mM and 9.2mM, respectively. MiR-133b showed up-regulation in HepG2 and miR-122-5p was down-regulated in HepG2 and Huh7 (29.5 and 1000 folds) in a dose dependent manner. MiR-26a-5p exhibited decrease in its level in both cell lines at IC35, but was increased at IC50 in HepG2 cells. MiR-518f-3p showed increase in its level during various doses of SB in both cell lines. Finally, miR-539-5p showed down expression in both cell lines. Prediction pathway analysis referred to the important role of each of miR-133b, miR-122-5p and miR-26a-5p in proliferation, apoptosis, angiogenesis and metastasis.
Conclusion: Sub-lethal doses of SB have significant effects on miRNAs expression in human hepatocellular car-cinoma cells. Understanding the epigenetic regulation of miRNAs may enhance the development of therapeutic strate-gies against HCC.