MicroRNA­122 regulation of the morphology and cytoarchitecture of hepatoma carcinoma cells.

MicroRNAs (miRNAs) are a large family of post­transcriptional regulators of gene expression that control a number of developmental and cellular processes in eukaryotic organisms and are ~23 nucleotides in length. miRNA­122 is an abundant liver­specific miRNA, implicated in fatty acid and cholesterol metabolism, as well as in hepatitis C viral replication and is frequently suppressed in primary hepatocellular carcinomas. In the current study, the Hep3B cell line with stable overexpression of miR­122 was successfully established through gene transfection methods and drug screening. miR­122 was observed to alter cell morphology in vitro by stable overexpression in Hep3B cells. This alteration was viewed by light microscopy and transmission electron microscopy. These alterations included increases in the cell volume, the appearance of lipid granules and vacuoles, thickening of nuclear membrane, swelling of the mitochondria, cytoplasm vacuolization and a more prominent nucleolus. Furthermore, the study provided novel evidence that miR­122 function was dependent upon its expression level. In addition, it was observed to negatively regulate mitochondria.

Effect of OSW-1 on microRNA expression profiles of hepatoma cells and functions of novel microRNAs.

3ß,16ß,17α-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-ß-D-xylopyranosyl)-(1→3)- (2-O-acet​yl-α-L-arabinopyranoside) (OSW-1) is a member of the cholestane saponin family, which was first isolated from the bulbs of Ornithogalum saundersiae and previously reported to be cytotoxic against several types of malignant cells. However, its antitumor mechanism remains unclear. Therefore, we investigated microRNA (miRNA) expression profiles in order to explore the antitumor activities of OSW-1. Furthermore, following study of differentially expressed miRNAs, the function of novel miRNAs and OSW-1 was determined using known miRNAs and anticarcinogens. The present study demonstrated that treatment with OSW-1 leads to the upregulation and downregulation of a large set of tumor-related miRNAs, including miR-299, miR-1908, miR-125b, miR-187a, miR-1275, hav1-miR-H6-3p, miR-181, miR-210, miR-483, miR-126, miR-208 and others. Notably, miR-141, miR-142, miR-200C and miR-1275 were found to be upregulated by OSW-1 and doxorubicine, as compared with doxorubicine alone. Additionally, the expression fold-change of miR-142-3P was ~58 times higher than its expression with a different treatment. These miRNAs are linked to cancer, including proliferation, differentiation, apoptosis, cell adhesion, migration, polarity and epithelial to mesenchymal transition (EMT).