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Small RNA expression from viruses, bacteria and human miRNAs in colon cancer tissue and its association with microsatellite instability and tumor location

ABSTRACT: BACKGROUND: MicroRNAs (miRNA) and other small RNAs are frequently dysregulated in cancer and are promising biomarkers for colon cancer. Here we profile human, virus and bacteria small RNAs in normal and tumor tissue from early stage colon cancer and correlate the expression with clinical p...

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Autores principales: Mjelle, Robin, Sjursen, Wenche, Thommesen, Liv, Sætrom, Pål, Hofsli, Eva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381638/
https://www.ncbi.nlm.nih.gov/pubmed/30786859
http://dx.doi.org/10.1186/s12885-019-5330-0
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author Mjelle, Robin
Sjursen, Wenche
Thommesen, Liv
Sætrom, Pål
Hofsli, Eva
author_facet Mjelle, Robin
Sjursen, Wenche
Thommesen, Liv
Sætrom, Pål
Hofsli, Eva
author_sort Mjelle, Robin
collection PubMed
description ABSTRACT: BACKGROUND: MicroRNAs (miRNA) and other small RNAs are frequently dysregulated in cancer and are promising biomarkers for colon cancer. Here we profile human, virus and bacteria small RNAs in normal and tumor tissue from early stage colon cancer and correlate the expression with clinical parameters. METHODS: Small RNAs from colon cancer tissue and adjacent normal mucosa of 48 patients were sequenced using Illumina high-throughput sequencing. Clinical parameters were correlated with the small RNA expression data using linear models. We performed a meta-analysis by comparing publicly available small RNA sequencing datasets with our original sequencing data to confirm the main findings. RESULTS: We identified 331 differentially expressed miRNAs between tumor and normal samples. We found that the major changes in miRNA expression between left and right colon are due to miRNAs located within the Hox-developmental genes, including miR-10b, miR-196b and miR-615. Further, we identified new miRNAs associated with microsatellite instability (MSI), including miR-335, miR-26 and miR-625. We performed a meta-analysis on all publicly available miRNA-seq datasets and identified 117 common miRNAs that were differentially expressed between tumor and normal tissue. The miRNAs miR-135b and miR-31 were the most significant upregulated miRNA in tumor across all datasets. The miRNA miR-133a was the most strongly downregulated miRNA in our dataset and also showed consistent downregulation in the other datasets. The miRNAs associated with MSI and tumor location in our data showed similar changes in the other datasets. Finally, we show that small RNAs from Epstein-Barr virus and Fusobacterium nucleatum are differentially expressed between tumor and normal adjacent tissue. CONCLUSIONS: Small RNA profiling in colon cancer tissue revealed novel RNAs associated with MSI and tumor location. We show that Fusobacterium nucleatum are detectable at the RNA-level in colon tissue, and that both Fusobacterium nucleatum and Epstein-Barr virus separate tumor and normal tissue. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-5330-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-63816382019-02-28 Small RNA expression from viruses, bacteria and human miRNAs in colon cancer tissue and its association with microsatellite instability and tumor location Mjelle, Robin Sjursen, Wenche Thommesen, Liv Sætrom, Pål Hofsli, Eva BMC Cancer Research Article ABSTRACT: BACKGROUND: MicroRNAs (miRNA) and other small RNAs are frequently dysregulated in cancer and are promising biomarkers for colon cancer. Here we profile human, virus and bacteria small RNAs in normal and tumor tissue from early stage colon cancer and correlate the expression with clinical parameters. METHODS: Small RNAs from colon cancer tissue and adjacent normal mucosa of 48 patients were sequenced using Illumina high-throughput sequencing. Clinical parameters were correlated with the small RNA expression data using linear models. We performed a meta-analysis by comparing publicly available small RNA sequencing datasets with our original sequencing data to confirm the main findings. RESULTS: We identified 331 differentially expressed miRNAs between tumor and normal samples. We found that the major changes in miRNA expression between left and right colon are due to miRNAs located within the Hox-developmental genes, including miR-10b, miR-196b and miR-615. Further, we identified new miRNAs associated with microsatellite instability (MSI), including miR-335, miR-26 and miR-625. We performed a meta-analysis on all publicly available miRNA-seq datasets and identified 117 common miRNAs that were differentially expressed between tumor and normal tissue. The miRNAs miR-135b and miR-31 were the most significant upregulated miRNA in tumor across all datasets. The miRNA miR-133a was the most strongly downregulated miRNA in our dataset and also showed consistent downregulation in the other datasets. The miRNAs associated with MSI and tumor location in our data showed similar changes in the other datasets. Finally, we show that small RNAs from Epstein-Barr virus and Fusobacterium nucleatum are differentially expressed between tumor and normal adjacent tissue. CONCLUSIONS: Small RNA profiling in colon cancer tissue revealed novel RNAs associated with MSI and tumor location. We show that Fusobacterium nucleatum are detectable at the RNA-level in colon tissue, and that both Fusobacterium nucleatum and Epstein-Barr virus separate tumor and normal tissue. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-5330-0) contains supplementary material, which is available to authorized users. BioMed Central 2019-02-20 /pmc/articles/PMC6381638/ /pubmed/30786859 http://dx.doi.org/10.1186/s12885-019-5330-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Mjelle, Robin
Sjursen, Wenche
Thommesen, Liv
Sætrom, Pål
Hofsli, Eva
Small RNA expression from viruses, bacteria and human miRNAs in colon cancer tissue and its association with microsatellite instability and tumor location
title Small RNA expression from viruses, bacteria and human miRNAs in colon cancer tissue and its association with microsatellite instability and tumor location
title_full Small RNA expression from viruses, bacteria and human miRNAs in colon cancer tissue and its association with microsatellite instability and tumor location
title_fullStr Small RNA expression from viruses, bacteria and human miRNAs in colon cancer tissue and its association with microsatellite instability and tumor location
title_full_unstemmed Small RNA expression from viruses, bacteria and human miRNAs in colon cancer tissue and its association with microsatellite instability and tumor location
title_short Small RNA expression from viruses, bacteria and human miRNAs in colon cancer tissue and its association with microsatellite instability and tumor location
title_sort small rna expression from viruses, bacteria and human mirnas in colon cancer tissue and its association with microsatellite instability and tumor location
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381638/
https://www.ncbi.nlm.nih.gov/pubmed/30786859
http://dx.doi.org/10.1186/s12885-019-5330-0
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