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

Abstract

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 cutoff 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.

Sp1 transcription factor represses transcription of phosphatase and tensin homolog to aggravate lung injury in mice with type 2 diabetes mellitus-pulmonary tuberculosis

“…PTEN has been documented to play a key role in resisting infections by bacillus Calmette-Guérin and Mycoplasma in mammalian cells [ 21 ]. In a work by Lu et al ., PTEN was identified as one of the four key factors mediated by the differentially expressed microRNAs between patients with and without latent tuberculosis infections [ 36 ]. However, the specific role of PTEN in Mtb infection remains unexplained.…”

Benefits and Challenges of Pre-clustered Network-Based Pathway Analysis

“…Due to the ubiquitous use of pathway analysis methods and reliance on their output to interpret results from diverse and important fields of research such as drug development ( Jhamb et al, 2019 ), biomarker discovery ( Chen et al, 2017 ) and patient diagnosis ( Lu et al, 2019 ), it is important to ensure that these methods can cope well with complex gene sets.…”

Associations of genetic variants of miRNA coding regions with pulmonary tuberculosis risk in China

“…During MTB infection, which lies at the root of active TB disease in humans, downregulated expression of microRNAs homo sapiens (hsa)-miR-29a and hsa-miR-15b has been reported [4]. By contrast, hsa-miR-576-5p, hsa-miR-500 and hsa-miR-155 expression have been shown to be upregulated during latent tuberculosis infection (LTBI) [3]. Intriguingly, miRNA effects have been demonstrated during different stages of TB progression; for example, Beibei Fu et al found that miR-325-3p was upregulated after MTB infection then demonstrated that miR-325-deficient mice exhibited MTB resistance [5].…”

“…In addition, host molecular regulatory mechanisms, such as gene-expression regulation by microRNAs (miRNAs), may also be involved in disease progression. As a class of non-coding ribonucleic acids (RNAs)，miRNAs play key roles in regulating post-transcriptional gene expression during numerous physiological and pathological processes, including MTB infection and TB progression to active disease [3]. During MTB infection, which lies at the root of active TB disease in humans, downregulated expression of miRNAs homo sapiens (hsa)-miR-29a and hsa-miR-15b has been reported [4].…”