The Effect of Methylselenocysteine and Sodium Selenite Treatment on microRNA Expression in Liver Cancer Cell Lines

The unique character of selenium compounds, including sodium selenite and Se-methylselenocysteine (MSC), is that they exert cytotoxic effects on neoplastic cells, providing a great potential for treating cancer cells being highly resistant to cytostatic drugs. However, selenium treatment may affect microRNA (miRNA) expression as the pattern of circulating miRNAs changed in a placebo-controlled selenium supplement study. This necessitates exploring possible changes in the expression profiles of miRNAs. For this, miRNAs being critical for liver function were selected and their expression was measured in hepatocellular carcinoma (HLE and HLF) and cholangiocarcinoma cell lines (TFK-1 and HuH-28) using individual TaqMan MicroRNA Assays following selenite or MSC treatments. For establishing tolerable concentrations, IC(50)values were determined by performing SRB proliferation assays. The results revealed much lower IC(50)values for selenite (from 2.7 to 11.3 mu M) compared to MSC (from 79.5 to 322.6 mu M). The treatments resulted in cell line-dependent miRNA expression patterns, with all miRNAs found to show fold change differences; however, only a few of these changes were statistically different in treated cells compared to untreated cells below IC50. Namely, miR-199a in HLF, miR-143 in TFK-1 upon MSC treatment, miR-210 in HLF and TFK-1, miR-22, -24, -122, -143 in HLF upon selenite treatment. Fold change differences revealed that miR-122 with both selenium compounds, miR-199a with MSC and miR-22 with selenite were affected. The miRNAs showing minimal alterations included miR-125b and miR-194. In conclusion, our results revealed moderately altered miRNA expression in the cell lines (less alterations following MSC treatment), being miR-122, -199a the most affected and miR-125b, -194 the least altered miRNAs upon selenium treatment.