ABSTRACT

Microcystin-leucine arginine (MC-LR), an important hepatoxin, has the effect of promoting hepatocarcinogenesis. MicroRNA-122 (miR-122), an important tumor suppressor in liver, plays an important role in promoting cell apoptosis. Previous studies found that the expression of miR-122 was reduced after MC-LR exposure in liver. In this study, C57BL/6 mice were exposed to saline, negative control agomir, and MC-LR with or without miR-122 agomir transfection. The results indicated that MC-LR promoted the expressions of tumor suppressor genes and decreased the expressions of anti-apoptotic proteins B cell lymphoma-2 (Bcl-2) and Bcl-2-like 2 (Bcl-w), causing hepatocyte apoptosis. Under MC-LR exposure, miR-122 agomir transfection could further increase the expressions of tumor suppressor genes and the release of cytochrome-c (Cyt-c) and decrease the expressions of Bcl-2 and Bcl-w. In conclusion, miR-122 reduction can mitigate MC-LR-induced apoptosis to a certain extent, which in turn, it is likely to have contributed to MC-LR-induced hepatocarcinogenesis.

摘要

微囊藻毒素-亮氨酸精氨酸（MC-LR）是一种重要的肝毒素，具有促进肝癌发生的作用。MicroRNA-122（miR-122）是肝脏中重要的肿瘤抑制因子，在促进细胞凋亡中起重要作用。先前的研究发现，在肝脏中 MC-LR 暴露后 miR-122 的表达降低。在这项研究中，C57BL/6 小鼠暴露于盐水、阴性对照 agomir 和 MC-LR，有或没有 miR-122 agomir 转染。结果表明，MC-LR促进抑癌基因的表达，降低抗凋亡蛋白B细胞淋巴瘤-2（Bcl-2）和Bcl-2-like 2（Bcl-w）的表达，引起肝细胞凋亡。在 MC-LR 曝光下，转染miR-122 agomir可以进一步增加抑癌基因的表达和细胞色素-c（Cyt-c）的释放，降低Bcl-2和Bcl-w的表达。总之，miR-122的减少可以在一定程度上减轻MC-LR诱导的细胞凋亡，这反过来可能有助于MC-LR诱导的肝癌发生。