miR-96 exerts carcinogenic effect by activating AKT/GSK-3β/β-catenin signaling pathway through targeting inhibition of FOXO1 in hepatocellular carcinoma

作者：Nanmu Yang, Jinxue Zhou, Qingjun Li, Feng Han, Zujiang Yu · 发表于：Cancer Cell International · 年份：2019 · DOI：10.1186/s12935-019-0756-7 · 被引用次数：27 · 研究领域：FOXO transcription factor regulation、MicroRNA in disease regulation、Circular RNAs in diseases

The aim of this research was to investigate the mechanism of miR-96 affecting hepatocellular carcinoma (HCC). mRNA and protein expression was detected by qRT-PCR and Western blot, respectively. HepG2 cells were transfected and grouped as follows: miR-NC group, miR-mimics group, NC + Vector group, mimics + Vector group, mimics + FOXO1 group. Luciferase reporter assay was performed. MTT and Transwell assay was conducted. In vivo studies by nude mice were performed. Immunohistochemistry and immunofluorescence was executed. Up-regulated miR-96 and down-regulated FOXO1 was found in tumor tissues and HepG2 cells ( P < 0.01). FOXO1 was directly suppressed by miR-96. Compared with NC + Vector group, mimics + Vector group has higher OD495 value ( P < 0.05), higher migration and invasion cells ( P < 0.01), larger transplanted tumor volume ( P < 0.01), lower FOXO1 positive cell numbers ( P < 0.01), higher p-AKT and p-GSK-3β expression ( P < 0.01), lower p-β-catenin expression ( P < 0.01), more β-catenin expression in the nucleus ( P < 0.01). Compared with mimics + Vector group, mimics + FOXO1 group has lower OD495 value ( P < 0.05), lower migration and invasion cells (P < 0.01), smaller transplanted tumor volume ( P < 0.01), higher FOXO1 positive cells ( P < 0.01), lower p-AKT and p-GSK-3β expression ( P < 0.01), higher p-β-catenin expression ( P < 0.01), less β-catenin expression in the nucleus ( P < 0.01). miR-96 exerts carcinogenic effect by activating AKT/GSK-3β/β-catenin signaling ...