Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis

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.

Overexpression of chaperonin containing TCP1 subunit 7 has diagnostic and prognostic value for hepatocellular carcinoma

“…In addition, the knockdown of CCT3 was shown to inhibit the activation of signal transducer and activator of transcription 3. Xu and colleagues reported that CCT5 was the direct target of miR-139-5p and promoted the progression of HCC through the spliceosome pathway [35]. To the best of our knowledge, no previous studies have described the molecular mechanisms of CCT7 activity in HCC; however, consistent with the known functions of CCT3 and CCT5 in HCC, our study revealed that CCT7 promotes the progression of HCC through the spliceosome pathway.…”

Construction and Comprehensive Analysis of a circRNA-miRNA-mRNA Regulatory Network to Reveal the Pathogenesis of Hepatocellular Carcinoma

“…Furthermore, accumulated evidence has demonstrated that multiple molecules mediated the tumorigenesis and metastasis of HCC by regulating the YWHAZ -associated axis ( Zhao et al, 2018 ; Wei et al, 2019 ; Liu et al, 2020a ; Shen et al, 2020 ). Bioinformatic analysis also revealed the miR-139-5p/ CCT5 axis might exert a momentous effect on HCC progression, but in-depth validated studies have not been carried out ( Xu et al, 2021 ). As for DDX39B , its functions in HCC progression have not been studied yet.…”

Use of miRNA Sequencing to Reveal Hub miRNAs and the Effect of miR-582-3p/SMAD2 in the Progression of Hepatocellular Carcinoma

“…Li found that microrNA-582-3p negatively regulates cell proliferation and cell cycle progression in acute myeloid leukemia Targeting cyclin B2 ( Li H. et al, 2019 ). In hepatocellular carcinoma, miR-139-5p can regulate the proliferation, migration and invasion of hepatocellular carcinoma cells by targeting different targets such as SLITRK4 ( Wu et al,2020 ), CCT5 ( Xu et al,2021 ) and ARF6 ( Wu et al,2021 ). However, there have been relatively few studies on hepatocellular carcinoma mediated by miR-582-3p.…”