MicroRNA-16 participates in the cell cycle alteration of HepG2 cells induced by MC-LR

Abstract

Microcystin-LR (MC-LR) is a cyclic hepatotoxin produced by cyanobacteria in freshwater, and chronic MC-LR exposure could induce human hepatitis if consumed in drinking water. In recent years, many studies have indicated that microRNAs participate in the hepatotoxicity of MC-LR. The purpose of this study was to investigate the potential function of miR-16 in the hepatocellular toxicity and cell cycle alteration induced by MC-LR in human hepatocellular carcinoma (HepG2) cells after treatment with 10 μM MC-LR. The result of flow cytometry detection showed that a low concentration of MC-LR (10 μM) failed to induce apoptosis but promoted cell cycle G1/S transition in HepG2 cells. In addition, the expression of apoptosis-related genes was suppressed after MC-LR exposure. These results confirm that MC-LR exposure at a low dose can promote the proliferation of HepG2 cells. Furthermore, we also found that microRNA-16 (miR-16) expression was suppressed in HepG2 cells following MC-LR exposure. Hence, we overexpressed miR-16 in HepG2 cells and treated them with MC-LR, and the results showed that miR-16 overexpression induced an increase in the G0/G1 phase and a decrease in the S phase cell cycle populations in HepG2 cells, suggesting that miR-16 can inhibit the cell proliferation of HepG2 cells. In conclusion, our results suggest that miR-16 may play a vital role in the cell cycle alteration of HepG2 cells after MC-LR exposure.

Keywords: Cell cycle; Cell proliferation; HepG2 cells; Microcystin-LR; miR-16.