He Yujiao, Huang Maolin, Tang Chunyan, Yue Yan, Liu Xiao, Zheng Zhebin, Dong Hongbo, Liu Deming
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, Sichuan, 610106, PR China.
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, Sichuan, 610106, PR China.
Virus Res. 2021 Jun;298:198404. doi: 10.1016/j.virusres.2021.198404. Epub 2021 Mar 26.
MicroRNAs are emerging as critical endogenous regulators of gene function. Aberrant regulation of microRNAs is associated with various human diseases, most importantly cancer. MicroRNA-122 (miR-122), a liver-specific microRNA, has been implicated in the control of hepatitis C virus (HCV) RNA replication and its response to interferon (IFN) in human hepatoma cells. Here, we report that daidzein, a naturally occurring plant isoflavone, inhibits HCV replication and enhances the antiviral effect of IFN-α on HCV therapy by decreasing microRNA-122 levels in vitro without significantly affecting cell growth. Moreover, daidzein was found to inhibit the expression of miR-122 and miR-21 by down-regulating the expression of TRBP, indicating that daidzein is possibly a general inhibitor of the miRNA pathway. Thus, daidzein provides new insights for drug discovery and HCV prevention.
微小RNA正成为基因功能的关键内源性调节因子。微小RNA的异常调节与多种人类疾病相关,其中最重要的是癌症。微小RNA-122(miR-122)是一种肝脏特异性微小RNA,已被证明在人类肝癌细胞中参与丙型肝炎病毒(HCV)RNA复制的控制及其对干扰素(IFN)的反应。在此,我们报告大豆苷元,一种天然存在的植物异黄酮,在体外通过降低微小RNA-122水平抑制HCV复制并增强IFN-α对HCV治疗的抗病毒作用,且对细胞生长无显著影响。此外,发现大豆苷元通过下调TRBP的表达来抑制miR-122和miR-21的表达,表明大豆苷元可能是微小RNA途径的通用抑制剂。因此,大豆苷元为药物研发和HCV预防提供了新的见解。