MicroRNA-23C Impacts Hepatocellular Carcinoma Metastasis by Targeting OTUB1

MicroRNA-23C (miR-23C) and Ovarian Tumor domain-containing Ubiquitin Aldehyde-Binding protein 1 (OTUB1) have been crucially implicated in numerous malignancies, such as Hepatocellular Carcinoma (HCC), a common malignant tumor. Herein, the function of the miR-23C-OTUB1-PI3K/AKT signaling pathway in HCC cell aggressiveness and Epithelial-Mesenchymal Transition (EMT) was explored, potentially revealing novel therapeutic approaches or targets for HCC.

miR-23C expression was predicted and confirmed using bioinformatics analysis and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), respectively. The findings suggest miR-23C suppression was evaluated via the Cell Counting Kit 8 (CCK8), Transwell invasion, and wound healing assays. Western Blotting (WB) was employed to analyze EMT-related protein expression and the phosphorylation level of AKT (AK strain transforming). Target genes and binding sites were predicted using bioinformatics analysis, and their validation was confirmed by a dual-luciferase assay. The in vivo regulatory impact of miR-23C on target genes was confirmed using a model of nude mouse xenograft.

Both HCC tissues and cells exhibited miR-23C downregulation. While OTUB1 overexpression promoted HCC cell invasion, migration, and EMT, its knockdown, along with miR-23C upregulation, exerted a contrary effect. We further identified OTUB1 as a target gene of miR-23C, and in vivo experiments confirmed that miR-23C negatively regulated OTUB1 expression. Additionally, OTUB1 overexpression increased AKT phosphorylation, a phenomenon that was inhibited by OTUB1 silencing or transfection with the miR-23C mimic. Moreover, co-overexpression of OTUB1 and the miR-23C mimic counteracted the OTUB1 effects.

Our findings show miR-23C may suppress Hepatocellular Carcinoma (HCC) metastasis in experimental models by directly targeting OTUB1, potentially contributing to the inactivation of the PI3K/AKT pathway. These preliminary findings suggest that the miR-23C/OTUB1/AKT axis may warrant further investigation as a potential therapeutic target.

Overall, in our preclinical models, miR-23C appeared to inhibit HCC cell aggressiveness and EMT by targeting OTUB1 and potentially regulating the PI3K/AKT pathway.