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Bioinformatics analysis of microRNA expression between patients with and without latent tuberculosis infections

Tuberculosis (TB) is a globally prevalent infectious disease. The mechanisms of latent TB infection (LTBI) remain to be fully elucidated and may provide novel approaches for diagnosis. As therapeutic targets and molecular diagnostic markers, microRNAs (miRs) have been studied and utilized in various...

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Autores principales: Lu, Yang, Wang, Xinmin, Dong, Hongchang, Wang, Xiaofang, Yang, Pu, Han, Ling, Wang, Yingzi, Zheng, Zhihong, Zhang, Wanjiang, Zhang, Le
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447890/
https://www.ncbi.nlm.nih.gov/pubmed/30988779
http://dx.doi.org/10.3892/etm.2019.7424
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author Lu, Yang
Wang, Xinmin
Dong, Hongchang
Wang, Xiaofang
Yang, Pu
Han, Ling
Wang, Yingzi
Zheng, Zhihong
Zhang, Wanjiang
Zhang, Le
author_facet Lu, Yang
Wang, Xinmin
Dong, Hongchang
Wang, Xiaofang
Yang, Pu
Han, Ling
Wang, Yingzi
Zheng, Zhihong
Zhang, Wanjiang
Zhang, Le
author_sort Lu, Yang
collection PubMed
description Tuberculosis (TB) is a globally prevalent infectious disease. The mechanisms of latent TB infection (LTBI) remain to be fully elucidated and may provide novel approaches for diagnosis. As therapeutic targets and molecular diagnostic markers, microRNAs (miRs) have been studied and utilized in various diseases. In the present study, the differentially expressed miRs (DEMs) in LTBI were screened and analyzed to determine the underlying mechanisms and identify potential biomarkers, thereby contributing to the diagnosis of LTBI. The GSE25435 and GSE29190 datasets from Gene Expression Omnibus were selected for analysis. The 2 datasets were analyzed individually using the Bioconductor package to screen the DEMs with specific cut-off criteria [P<0.01 and |log (fold change)|≥1]. Target gene prediction and interaction network construction were performed using Targetscan, the Search Tool for the Retrieval of Interacting Genes and Proteins and Cytoscape individually, and were merged using the latter tool. The hub genes were finally selected based on their degree of connectivity (DC). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the KEGG and GENCLIP. A total of 144 DEMs were identified from the 2 datasets. By exploring the overlapping miRs in the two datasets, Homo sapiens (hsa)-miR-29a and hsa-miR-15b were identified to be decreased, while hsa-miR-576-5p, hsa-miR-500 and hsa-miR-155 were identified to be upregulated. hsa-miR-500a-3p and hsa-miR-29a-3p, as well as 4 genes, namely cell division cycle (CDC)42, actin α1, skeletal muscle (ACTA1), phosphatase and tensin homolog (PTEN) and fos proto-oncogene (FOS), were selected as the key factors in this regulatory network. A total of 9 signaling pathways, including phosphoinositide-3 kinase (PI3K)/AKT and 11 biological processes, were identified to be associated with LTBI. In conclusion, the present analysis identified hsa-miR-500a-3p and hsa-miR-29a-3p, as well as CDC42, ACTA1, PTEN and FOS, as the most promising biomarkers and therapeutic candidates for LTBI. The PI3K/AKT signaling pathway is the key signaling pathway implicated in LTBI, and an in-depth investigation of the efficiency of PI3K/AKT signaling inhibitors may be used to prevent a chronic state of infection in LTBI.
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spelling pubmed-64478902019-04-15 Bioinformatics analysis of microRNA expression between patients with and without latent tuberculosis infections Lu, Yang Wang, Xinmin Dong, Hongchang Wang, Xiaofang Yang, Pu Han, Ling Wang, Yingzi Zheng, Zhihong Zhang, Wanjiang Zhang, Le Exp Ther Med Articles Tuberculosis (TB) is a globally prevalent infectious disease. The mechanisms of latent TB infection (LTBI) remain to be fully elucidated and may provide novel approaches for diagnosis. As therapeutic targets and molecular diagnostic markers, microRNAs (miRs) have been studied and utilized in various diseases. In the present study, the differentially expressed miRs (DEMs) in LTBI were screened and analyzed to determine the underlying mechanisms and identify potential biomarkers, thereby contributing to the diagnosis of LTBI. The GSE25435 and GSE29190 datasets from Gene Expression Omnibus were selected for analysis. The 2 datasets were analyzed individually using the Bioconductor package to screen the DEMs with specific cut-off criteria [P<0.01 and |log (fold change)|≥1]. Target gene prediction and interaction network construction were performed using Targetscan, the Search Tool for the Retrieval of Interacting Genes and Proteins and Cytoscape individually, and were merged using the latter tool. The hub genes were finally selected based on their degree of connectivity (DC). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the KEGG and GENCLIP. A total of 144 DEMs were identified from the 2 datasets. By exploring the overlapping miRs in the two datasets, Homo sapiens (hsa)-miR-29a and hsa-miR-15b were identified to be decreased, while hsa-miR-576-5p, hsa-miR-500 and hsa-miR-155 were identified to be upregulated. hsa-miR-500a-3p and hsa-miR-29a-3p, as well as 4 genes, namely cell division cycle (CDC)42, actin α1, skeletal muscle (ACTA1), phosphatase and tensin homolog (PTEN) and fos proto-oncogene (FOS), were selected as the key factors in this regulatory network. A total of 9 signaling pathways, including phosphoinositide-3 kinase (PI3K)/AKT and 11 biological processes, were identified to be associated with LTBI. In conclusion, the present analysis identified hsa-miR-500a-3p and hsa-miR-29a-3p, as well as CDC42, ACTA1, PTEN and FOS, as the most promising biomarkers and therapeutic candidates for LTBI. The PI3K/AKT signaling pathway is the key signaling pathway implicated in LTBI, and an in-depth investigation of the efficiency of PI3K/AKT signaling inhibitors may be used to prevent a chronic state of infection in LTBI. D.A. Spandidos 2019-05 2019-03-20 /pmc/articles/PMC6447890/ /pubmed/30988779 http://dx.doi.org/10.3892/etm.2019.7424 Text en Copyright: © Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Lu, Yang
Wang, Xinmin
Dong, Hongchang
Wang, Xiaofang
Yang, Pu
Han, Ling
Wang, Yingzi
Zheng, Zhihong
Zhang, Wanjiang
Zhang, Le
Bioinformatics analysis of microRNA expression between patients with and without latent tuberculosis infections
title Bioinformatics analysis of microRNA expression between patients with and without latent tuberculosis infections
title_full Bioinformatics analysis of microRNA expression between patients with and without latent tuberculosis infections
title_fullStr Bioinformatics analysis of microRNA expression between patients with and without latent tuberculosis infections
title_full_unstemmed Bioinformatics analysis of microRNA expression between patients with and without latent tuberculosis infections
title_short Bioinformatics analysis of microRNA expression between patients with and without latent tuberculosis infections
title_sort bioinformatics analysis of microrna expression between patients with and without latent tuberculosis infections
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447890/
https://www.ncbi.nlm.nih.gov/pubmed/30988779
http://dx.doi.org/10.3892/etm.2019.7424
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