College of Life Science, Henan Normal University, Xinxiang, Henan, 453007, China.
College of Life Science, Henan Normal University, Xinxiang, Henan, 453007, China.
Ecotoxicol Environ Saf. 2020 Apr 1;192:110295. doi: 10.1016/j.ecoenv.2020.110295. Epub 2020 Feb 14.
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.
微囊藻毒素-LR（MC-LR）是一种在淡水中由蓝藻产生的环型肝毒素，如果在饮用水中摄入，慢性 MC-LR 暴露可能会导致人类肝炎。近年来，许多研究表明 microRNAs 参与了 MC-LR 的肝毒性。本研究旨在探讨 miR-16 在 10μM MC-LR 处理人肝癌细胞（HepG2）后，MC-LR 诱导的肝细胞毒性和细胞周期改变中的潜在作用。流式细胞术检测结果表明，低浓度 MC-LR（10μM）未能诱导细胞凋亡，但促进 HepG2 细胞周期 G1/S 期转变。此外，MC-LR 暴露后凋亡相关基因的表达受到抑制。这些结果证实，MC-LR 低剂量暴露可促进 HepG2 细胞的增殖。此外，我们还发现 MC-LR 暴露后 HepG2 细胞中 microRNA-16（miR-16）的表达受到抑制。因此，我们在 HepG2 细胞中转染 miR-16 并给予 MC-LR 处理，结果显示 miR-16 过表达诱导 HepG2 细胞中 G0/G1 期细胞比例增加和 S 期细胞比例减少，表明 miR-16 可抑制 HepG2 细胞的增殖。总之，我们的研究结果表明，miR-16 可能在 MC-LR 暴露后 HepG2 细胞周期改变中发挥重要作用。
