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Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis
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 t...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436101/ https://www.ncbi.nlm.nih.gov/pubmed/34522182 http://dx.doi.org/10.7150/ijms.57504 |
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author | Xu, Jingjing Zhang, Yuan Liu, Cheng Yan, Ping Yang, Zongguo |
author_facet | Xu, Jingjing Zhang, Yuan Liu, Cheng Yan, Ping Yang, Zongguo |
author_sort | Xu, Jingjing |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8436101 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-84361012021-09-13 Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis Xu, Jingjing Zhang, Yuan Liu, Cheng Yan, Ping Yang, Zongguo Int J Med Sci Research Paper 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. Ivyspring International Publisher 2021-08-25 /pmc/articles/PMC8436101/ /pubmed/34522182 http://dx.doi.org/10.7150/ijms.57504 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Xu, Jingjing Zhang, Yuan Liu, Cheng Yan, Ping Yang, Zongguo Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis |
title | Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis |
title_full | Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis |
title_fullStr | Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis |
title_full_unstemmed | Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis |
title_short | Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis |
title_sort | roles of the mir-139-5p/cct5 axis in hepatocellular carcinoma: a bioinformatic analysis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436101/ https://www.ncbi.nlm.nih.gov/pubmed/34522182 http://dx.doi.org/10.7150/ijms.57504 |
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