MicroRNA hsa-miR-29a-3p is a plasma biomarker for the differential diagnosis and monitoring of tuberculosis

Ndzi, Elvis Ndukong; Nkenfou, Céline Nguefeu; Mekue, Linda Mouafo; Zentilin, Lorena; Tamgue, Ousman; Pefura, E.W.; Kuiaté, Jules Roger; Giacca, Mauro; Ndjolo, Alexis

doi:10.1016/j.tube.2018.12.001

Cited by 53 publications

(51 citation statements)

References 13 publications

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“…Microarray analysis has been widely used to investigate DEMs, dysregulated genes and pathways associated with LTBI (21,30,31). In previous decades, a large amount of research investigating this matter has emerged (18,(32)(33)(34); however, identifying novel miRs can be used to investigate further the underlying mechanism of LTBI. Thus, in the present study, expression data obtained from patients with and without LTBI were subjected to a bioinformatics analysis to provide more reliable data.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Dong

et al. 2019

Exp Ther Med

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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.

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Section: Discussionmentioning

confidence: 99%

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

Wang

Dong

et al. 2019

Exp Ther Med

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“…Nonetheless, notwithstanding the heterogeneity of the results, some miRNAs have been recurrently identified as candidate biomarkers of TB in more than one study. Among these candidate miRNAs, miR-26a-5p, and miR-29a-3p were identified by different studies as significantly overexpressed in patients with active TB vs. healthy controls [ 86 , 88 , 90 , 108 , 109 , 115 ]. These are relevant miRNAs in TB pathogenesis, since, as previously discussed, both directly or indirectly target IFNγ, thus suppressing host innate and adaptive immune response against intracellular pathogens.…”

Section: Biomarker Discovery Studiesmentioning

confidence: 99%

“…Other anti-inflammatory miRNA, miR-21-5p, and miR-146a-5p, which are overexpressed in active TB patients, are promising diagnostic biomarker to differentiate between active TB and latent infection or an healthy condition [ 87 , 92 , 101 ]. MiR-155-5p, overexpressed in TB patients and candidate biomarker of active TB, plays a key role in host defense against M. tuberculosis [ 86 , 96 , 112 ].…”

Section: Biomarker Discovery Studiesmentioning

confidence: 99%

“…Since the currently available tests do not effectively discriminate between LTBI and active TB, a biomarker with a significant difference in expression between the two conditions would be very useful. Several studies of miRNA expression profiling in serum/plasma [ 86 , 90 , 97 , 102 ] or in blood cells [ 33 , 39 , 109 , 116 , 118 ] have been performed in cohorts which included subjects with LTBI along with active TB infection and healthy controls. In some of these studies, significant miRNA signatures were identified that could actually discriminate active TB from LTBI.…”

Section: Biomarker Discovery Studiesmentioning

confidence: 99%

“…The same experimental setup was used in another study that identified overexpression of miR-194-5p, miR-21-5p, miR-29c-3p and the downregulation of miR-150-5p in the active TB group compared with both LTBI and HC groups [ 100 ]. By using qRT-PCR, miR-29a-3p overexpression was confirmed to be a valuable candidate biomarker to discriminate between active TB and LTBI in a cohort of subjects from Cameroon [ 86 ]. In this cohort, expression levels of miRNAs was similar in subjects co-infected with HIV and in those without HIV infection [ 86 ].…”

Section: Biomarker Discovery Studiesmentioning

confidence: 99%

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Tuberculosis-Associated MicroRNAs: From Pathogenesis to Disease Biomarkers

Sinigaglia

Peta

Riccetti

et al. 2020

Cells

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Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the most lethal infectious diseases with estimates of approximately 1.4 million human deaths in 2018. M. tuberculosis has a well-established ability to circumvent the host immune system to ensure its intracellular survival and persistence in the host. Mechanisms include subversion of expression of key microRNAs (miRNAs) involved in the regulation of host innate and adaptive immune response against M. tuberculosis. Several studies have reported differential expression of miRNAs during active TB and latent tuberculosis infection (LTBI), suggesting their potential use as biomarkers of disease progression and response to anti-TB therapy. This review focused on the miRNAs involved in TB pathogenesis and on the mechanism through which miRNAs induced during TB modulate cell antimicrobial responses. An attentive study of the recent literature identifies a group of miRNAs, which are differentially expressed in active TB vs. LTBI or vs. treated TB and can be proposed as candidate biomarkers.

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