Abstract
Background: MiRNAs are pivotal regulators involved in proliferation, apoptosis, invasion, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, drug resistance and autophagy in hepatocellular carcinoma (HCC). The aim of this study was to investigate the influence of miR-139-5p and its target genes on the outcomes of HCC. Methods: Survival analysis of miR-139-5p in HCC was conducted in Kaplan-Meier plotter. Target genes of miR-139-5p were identified in TargetScan, miRTarBase and starBase. Gene Expression Omnibus (GEO) series were used for the validation of miR-139-5p target genes. Cox proportional regression model was also established. Results: In Kaplan-Meier plotter, 163 HCC patients were included. MiR-139-5p downregulation was significantly associated with unfavorable overall survival (OS) and disease-free survival (DFS) in HCC patients (all P < 0.001). MiR-139-5p was significantly downregulated in HCC tumors and human hepatoma cell lines (all P < 0.05). As a target gene of miR-139-5p, CCT5 was overexpressed in HCC tumor tissues and peripheral blood mononuclear cells (all P < 0.05). A negative correlation between CCT5 and miR-139-5p was found in TCGA dataset. CCT5 overexpression was significantly associated with worse OS in HCC patients (P < 0.001), which was validated in the GSE14520 dataset (P = 0.017). CCT5 mRNA was significantly overexpressed in HCC patients with alpha-fetoprotein (AFP) > 300 ng/ml, BCLC staging B-C, TNM staging III and main tumor size > 5 cm (all P < 0.05). According to the Cox regression model of CCT5-interacting genes, HCC patients with high risk had poor OS compared to those with low risk in the TCGA dataset (P < 0.001), with the 1-year, 3-year, and 5-year ROC curves of an area under the curve (AUC) equal to 0.704, 0.662, and 0.631, respectively. Conclusions: MiR-139-5p suppresses HCC tumor aggression and conversely correlated with CCT5. The miR-139-5p/CCT5 axis might perform crucial functions in the development of HCC.