Wang Rui, Liu Haohao, Du Xingde, Ma Ya, Tian Zhihui, Zhang Shiyu, Shi Linjia, Guo Hongxiang, Zhang Huizhen
College of Public Health, Zhengzhou University, Zhengzhou, Henan, P.R. China.
College of Life Sciences, Henan Agricultural University, Zhengzhou, Henan, P.R. China.
Int J Environ Health Res. 2022 Oct;32(10):2123-2134. doi: 10.1080/09603123.2021.1946489. Epub 2021 Jun 28.
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.
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。微小RNA - 122(miR - 122)是肝脏中一种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,肝脏暴露于MC - LR后miR - 122的表达降低。在本研究中,将C57BL / 6小鼠暴露于生理盐水、阴性对照激动剂以及转染或未转染miR - 122激动剂的MC - LR中。结果表明,MC - LR促进了肿瘤抑制基因的表达,降低了抗凋亡蛋白B细胞淋巴瘤 - 2(Bcl - 2)和Bcl - 2样蛋白2(Bcl - w)的表达,导致肝细胞凋亡。在MC - LR暴露下,miR - 122激动剂转染可进一步增加肿瘤抑制基因的表达和细胞色素c(Cyt - c)的释放,并降低Bcl - 2和Bcl - w的表达。总之,miR - 122表达降低可在一定程度上减轻MC - LR诱导的细胞凋亡,这反过来可能促进了MC - LR诱导的肝癌发生。