Mechanism underlying the targeted regulation of the SOD1 3′UTR by the AUF1/Dicer1/miR-155/SOD1 pathway in sodium arsenite-induced liver injury
Mechanism underlying the targeted regulation of the SOD1 3′UTR by the AUF1/Dicer1/miR-155/SOD1 pathway in sodium arsenite-induced liver injury
复制标题
AUF1/Dicer1/miR-155/SOD1通路靶向调控SOD1 3-UTR在亚砷酸钠诱导的肝损伤中的作用机制
DOI：
10.1016/j.ecoenv.2022.113990
复制
发表时间：
2022-08-20
影响因子：
6.8
通讯作者：
Hu, Yong
中科院分区：
文献类型：
--
作者：
Bi, Dingnian;Shi, Mingyang;Hu, Yong
Arsenic (As) is a natural hepatotoxicity inducer that is ubiquitous in water, soil, coal, and food. Studies have found that arsenite exposure elicits increased mRNA transcription and decreased protein expression of SOD1 in vivo and in vitro; however, the specific mechanisms remain unclear. Here, we established a model of arsenic -induced chronic liver injury by providing rats with drinking water containing different concentrations of so-dium arsenite (NaAsO2) and found that NaAsO2 exposure decreased the mRNA and protein levels of AUF1 and the protein level of SOD1 and elevated the mRNA and protein levels of Dicer1 and miR-155 and the mRNA level of SOD1. Overexpression of AUF1 under NaAsO2 stress in vitro induced Dicer1 mRNA and protein expression and decreased miR-155 levels, which could be reversed by AUF1 siRNA. In addition, miR-155 overexpression downregulated SOD1 mRNA and protein levels, although this change was inhibited after transfection with an miR-155 inhibitor. Taken together, our findings showed that NaAsO2 could upregulate Dicer1 mRNA and pro-tein, thereby increasing miR-155 expression by downregulating AUF1 mRNA and protein expression. A dual-luciferase reporter assay indicated that miR-155 decreased the mRNA and protein levels of SOD1 by targeting the SOD1 3 & PRIME;UTR, resulting in liver injury. This study provides an important research basis for further under-standing the factors underlying arsenic-induced liver injury to improve the prevention and control strategies for arsenism.
