Genistein Restricts the Epithelial Mesenchymal Transformation (EMT) and Stemness of Hepatocellular Carcinoma via Upregulating miR-1275 to Inhibit the EIF5A2/PI3K/Akt Pathway

作者：Xiao Yang, Wangjie Jiang, Xiangxu Kong, Xiao Zhou, Deming Zhu, Lianbao Kong · 发表于：Biology · 年份：2022 · DOI：10.3390/biology11101383 · 被引用次数：25 · 研究领域：MicroRNA in disease regulation、Cancer-related molecular mechanisms research、Circular RNAs in diseases

Purpose: Genistein is a natural phytoestrogen with various antitumor effects. In recent years, some microRNAs (miRNA) in cancer cells have been reported to be regulated by genistein. Our study focused on exploring the mechanisms of miRNA upregulation to inhibit the epithelial mesenchymal transformation (EMT) and stemness of hepatocellular carcinoma (HCC). Patients and Methods: MiR-1275 was discovered by the transcriptome sequencing of miRNA expression profiles in HepG2 cells treated with genistein or DMSO as a control. Then, we performed series functional experiments in vitro and vivo to explore the relationship between genistein and miR-1275 in HCC. The target gene (Eukaryotic initiation factor 5A2, EIF5A2) of miR-1275 was predicted by databases and finally determined by a dual luciferase reporter assay. The downstream signaling pathway of EIF5A2 was assessed by bioinformatics analysis and Western blot. Results: the inhibition of genistein on the viability of HCC cells was enhanced by the increase in treatment time and dose, but it had no obvious inhibitory effect on normal hepatocytes (QSG-7701). Through qRT-PCR and transcriptome sequencing, we discovered that miR-1275 was lowly expressed in HCC, and it can be raised by genistein. The overall survival (OS) and recurrence-free survival (RFS) of HCC patients with lowly expressed miR-1275 were lower than those of those with high expression levels. In vitro and vivo experiments exhibited that genistein and the overexpression of...