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In silico analysis of prognostic and diagnostic significance of target genes from prostate cancer cell lines derived exomicroRNAs
BACKGROUND: Cancer-secreted exovesicles are important for cell-to-cell communication by altering cancer-related signalling pathways. Exovesicles-derived miRNAs (exomiRNAs)-target genes can be useful for diagnostic and prognostic purposes. METHODS: ExomiRNA from prostate cancer (PCa) cells (PC-3 and...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10655318/ https://www.ncbi.nlm.nih.gov/pubmed/37978493 http://dx.doi.org/10.1186/s12935-023-03123-1 |
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author | Altuna-Coy, Antonio Ruiz-Plazas, Xavier Arreaza-Gil, Verónica Segarra-Tomás, José Chacón, Matilde R. |
author_facet | Altuna-Coy, Antonio Ruiz-Plazas, Xavier Arreaza-Gil, Verónica Segarra-Tomás, José Chacón, Matilde R. |
author_sort | Altuna-Coy, Antonio |
collection | PubMed |
description | BACKGROUND: Cancer-secreted exovesicles are important for cell-to-cell communication by altering cancer-related signalling pathways. Exovesicles-derived miRNAs (exomiRNAs)-target genes can be useful for diagnostic and prognostic purposes. METHODS: ExomiRNA from prostate cancer (PCa) cells (PC-3 and LNCaP) were quantified by qRT-PCR and compared to the healthy cell line RWPE-1 by using miRNome PCR 752 miRNAs Panel. MiRNet database was used to predict exomiRNA-target genes. ExomiRNA-target genes pathway functional enrichment was performed by using Reactome database and Enrichr platform. Protein–protein interaction analysis was carried out by using the STRING database. RNA target-gene sequencing data from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) database was screened out in 465 PCa patients for candidate gene expression in prostate tumour (PT) tissue and non-pathologic prostate (N-PP) tissue. Signature gene candidates were statistically analysed for diagnosis and prognosis usefulness. RESULTS: A total of 36 exomiRNAs were found downregulated when comparing PCa cells vs a healthy cell line; and when comparing PC-3 vs LNCaP, 14 miRNAs were found downregulated and 52 upregulated. Reactome pathway database revealed altered pathways and genes related to miRNA biosynthesis, miRNA-mediated gene silencing (TNRC6B and AGO1), and cell proliferation (CDK6), among others. Results showed that TNRC6B gene expression was up-regulated in PT tissue compared to N-PP (n = 52 paired samples) and could be useful for diagnostic purposes. Likewise, gene expression levels of CDK6, TNRC6B, and AGO1 were down-regulated in high-risk PT (n = 293) compared to low-risk PCa tissue counterparts (n = 172). When gene expression levels of CDK6, TNRC6B, and AGO1 were tested as a prognostic panel, the results showed that these improve the prognostic power of classical biomarkers. CONCLUSION: ExomiRNAs-targets genes, TNRC6B, CDK6, and AGO1, showed a deregulated expression profile in PCa tissue and could be useful for PCa diagnosis and prognosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03123-1. |
format | Online Article Text |
id | pubmed-10655318 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-106553182023-11-17 In silico analysis of prognostic and diagnostic significance of target genes from prostate cancer cell lines derived exomicroRNAs Altuna-Coy, Antonio Ruiz-Plazas, Xavier Arreaza-Gil, Verónica Segarra-Tomás, José Chacón, Matilde R. Cancer Cell Int Research BACKGROUND: Cancer-secreted exovesicles are important for cell-to-cell communication by altering cancer-related signalling pathways. Exovesicles-derived miRNAs (exomiRNAs)-target genes can be useful for diagnostic and prognostic purposes. METHODS: ExomiRNA from prostate cancer (PCa) cells (PC-3 and LNCaP) were quantified by qRT-PCR and compared to the healthy cell line RWPE-1 by using miRNome PCR 752 miRNAs Panel. MiRNet database was used to predict exomiRNA-target genes. ExomiRNA-target genes pathway functional enrichment was performed by using Reactome database and Enrichr platform. Protein–protein interaction analysis was carried out by using the STRING database. RNA target-gene sequencing data from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) database was screened out in 465 PCa patients for candidate gene expression in prostate tumour (PT) tissue and non-pathologic prostate (N-PP) tissue. Signature gene candidates were statistically analysed for diagnosis and prognosis usefulness. RESULTS: A total of 36 exomiRNAs were found downregulated when comparing PCa cells vs a healthy cell line; and when comparing PC-3 vs LNCaP, 14 miRNAs were found downregulated and 52 upregulated. Reactome pathway database revealed altered pathways and genes related to miRNA biosynthesis, miRNA-mediated gene silencing (TNRC6B and AGO1), and cell proliferation (CDK6), among others. Results showed that TNRC6B gene expression was up-regulated in PT tissue compared to N-PP (n = 52 paired samples) and could be useful for diagnostic purposes. Likewise, gene expression levels of CDK6, TNRC6B, and AGO1 were down-regulated in high-risk PT (n = 293) compared to low-risk PCa tissue counterparts (n = 172). When gene expression levels of CDK6, TNRC6B, and AGO1 were tested as a prognostic panel, the results showed that these improve the prognostic power of classical biomarkers. CONCLUSION: ExomiRNAs-targets genes, TNRC6B, CDK6, and AGO1, showed a deregulated expression profile in PCa tissue and could be useful for PCa diagnosis and prognosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03123-1. BioMed Central 2023-11-17 /pmc/articles/PMC10655318/ /pubmed/37978493 http://dx.doi.org/10.1186/s12935-023-03123-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Altuna-Coy, Antonio Ruiz-Plazas, Xavier Arreaza-Gil, Verónica Segarra-Tomás, José Chacón, Matilde R. In silico analysis of prognostic and diagnostic significance of target genes from prostate cancer cell lines derived exomicroRNAs |
title | In silico analysis of prognostic and diagnostic significance of target genes from prostate cancer cell lines derived exomicroRNAs |
title_full | In silico analysis of prognostic and diagnostic significance of target genes from prostate cancer cell lines derived exomicroRNAs |
title_fullStr | In silico analysis of prognostic and diagnostic significance of target genes from prostate cancer cell lines derived exomicroRNAs |
title_full_unstemmed | In silico analysis of prognostic and diagnostic significance of target genes from prostate cancer cell lines derived exomicroRNAs |
title_short | In silico analysis of prognostic and diagnostic significance of target genes from prostate cancer cell lines derived exomicroRNAs |
title_sort | in silico analysis of prognostic and diagnostic significance of target genes from prostate cancer cell lines derived exomicrornas |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10655318/ https://www.ncbi.nlm.nih.gov/pubmed/37978493 http://dx.doi.org/10.1186/s12935-023-03123-1 |
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