Differential Expression of Long Noncoding RNAs in Patients with Coronary Artery Disease (original) (raw)
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Frontiers in Tropical Diseases
Early diagnosis is crucial in controlling tuberculosis globally and in developing countries with the emergence of drug-resistant Mycobacterium tuberculosis strains. Long non-coding RNAs (lncRNAs) are promising tuberculosis diagnostic biomarkers. Two lncRNA diagnostic markers, lncRNA THRIL and lincRNA-p21, were studied as tuberculosis diagnostic biomarkers. This cross-sectional study was conducted at the Center of Respiratory Diseases of LAQUINTINIE hospital and the National Veterinary Laboratory of Douala from December 2020 to August 2021. The ability of lncRNAs to distinguish between 19 healthy controls, 15 latent tuberculosis, and 21 active tuberculosis was estimated using quantitative polymerase chain reaction and Receiver Operating Characteristic curve analysis. Our analysis showed that lncRNA THRIL and lincRNA-p21 were significantly upregulated (P <0.05) in active and latent tuberculosis compared with healthy controls. LincRNA-p21 expression was significantly increased (P &l...
mBio
In tuberculosis (TB), as in other infectious diseases, studies of small noncoding RNAs (sncRNA) in peripheral blood have focused on microRNAs (miRNAs) but have neglected the other major sncRNA classes in spite of their potential functions in host gene regulation. Using RNA sequencing of whole blood, we have therefore determined expression of miRNA, PIWI-interacting RNA (piRNA), small nucleolar RNA (snoRNA), and small nuclear RNA (snRNA) in patients with TB (n = 8), latent TB infection (LTBI; n = 21), and treated LTBI (LTBItt; n = 6) and in uninfected exposed controls (ExC; n = 14). As expected, sncRNA reprogramming was greater in TB than in LTBI, with the greatest changes seen in miRNA populations. However, substantial dynamics were also evident in piRNA and snoRNA populations. One miRNA and 2 piRNAs were identified as moderately accurate (area under the curve [AUC] = 0.70 to 0.74) biomarkers for LTBI, as were 1 miRNA, 1 piRNA, and 2 snoRNAs (AUC = 0.79 to 0.91) for accomplished LTB...
Frontiers in tropical diseases, 2022
Gaps in early and accurate diagnosis, effective drug control, and treatment monitoring are hindering the global eradication effort of tuberculosis. This infectious disease has become the deadliest worldwide before the outbreak of Covid-19. The search for new molecular biomarkers of tuberculosis will help to reverse this trend. Long non-coding RNAs (lncRNAs) have emerged as important regulators of the host immune response to infection, hence their link with the etiology and diagnosis of tuberculosis has attracted some attention from the research community. However, very little is known about their potential for the monitoring of tuberculosis treatment. This study aimed at assessing the potential of two lncRNAs: p50-associated Cyclooxygenase-2 Extragenic RNA (PACER) and Long Non-coding RNA 13 (LNC13) in the monitoring of tuberculosis treatment. This was a cross-sectional study carried out in Douala, Cameroon from December 2020 to August 2021. A quantitative real-time polymerase chain reaction followed by Cq analysis using the Livak method were performed to measure the relative expression levels of PACER and LNC13 in whole blood of healthy controls, patients with active pulmonary tuberculosis at the initiation of treatment, after two, five, and six months into treatment. Receiver Operating Characteristic curves analysis was Frontiers in Tropical Diseases frontiersin.org 01
Micro-RNA: A potential screening marker for latent tuberculosis
IP International Journal of Medical Microbiology and Tropical Diseases, 2023
Abstract An ancient disease, Tuberculosis is one of the most challenging infectious disease contributing to mortality and morbidity worldwide. Tuberculosis elimination globally, by 2050, is a mammoth task as Mycobacterial infections have wide range of presentation, from the clinical to the subclinical or latent and pose a diagnostic and therapeutic challenge. The virulence as well as evading property of Mycobacterium tuberculosisMtb) from the host's immune system confers upon it the ability to remain latent in the host cells. This forms the basis of classification of tuberculosis patient as having latent-TBI or active TB. This review focuses on the role of miRNA as biomarkers of LTBI. The aim is to have an overview of the current knowledge about miRNA, its involvement in TB pathogenesis and its role as a reliable tool for diagnosis of latent tuberculosis. miRNA are non-encoding endogenous RNAs which regulate gene expression by directing their target RNA for degradation or translational repression. Degraded RNA are released in the extracellular milieu, are present in various body fluids, such as blood, saliva, and urine, and are biomarkers for a number of diseases including cancer, Parkinsons’ disease, CAD, liver diseases, TB and other infectious diseases. miRNAs are differentially expressed during active TB and LTBI, and therefore can be used as biomarkers of disease progression and response to anti-TB therapy. This will further permit more specific therapeutic interventions in TB management. A thorough search of available literature resources was performed on online databases such as Google Scholar, NCBI, Nature, Research gate, PubMed, Science Direct. It was found that miRNA are promising biomarkers to identify healthy latent TB individuals for further course of action and can be reliable tools for routine use in current clinical practice for specific therapeutic interventions to limit active TB population. They meet the criteria of ideal biomarkers, such as minimally invasive, accessibility, high specificity, and sensitivity. Keywords: Biomarkers, Latent tuberculosis, miRNA, Pediatric, Diagnosis
Journal of Cellular and Molecular Medicine, 2017
Technological advances in RNA biology greatly improved transcriptome profiling during the last two decades. Besides the discovery of many small RNAs (sRNA) that are involved in the physiological and pathophysiological regulation of various cellular circuits, it becomes evident that the corresponding RNA genes might also serve as potential biomarkers to monitor the progression of disease and treatment. sRNA gene candidate npcTB_6715 was previously identified via experimental RNomic (unpublished data), and we report its application as potential biomarker for the detection of Mycobacterium tuberculosis (MTB) in patient samples. For proof of principle, we developed a multiplex PCR assay and report its validation with 500 clinical cultures, positive for Mycobacteria. The analysis revealed 98.9% sensitivity, 96.1% specificity, positive and negative predictive values of 98.6% and 96.8%, respectively. These results underscore the diagnostic value of the sRNA gene as diagnostic marker for the specific detection of MTB in clinical samples. Its successful application and the general ease of PCR-based detection compared to standard bacterial culture techniques might be the first step towards 'point-of-care' diagnostics of Mycobacteria. To the best of our knowledge, this is the first time for the design of diagnostic applications based on sRNA genes, in Mycobacteria.
Clinical & Translational Immunology, 2021
Objectives. Non-sputum-based tests to accurately identify active tuberculosis (TB) disease and monitor response to therapy are urgently needed. This study examined the biomarker capacity of a panel of plasma proteins alone, and in conjunction with a previously identified miRNA signature, to identify active TB disease. Methods. The expression of nine proteins (IP-10, MCP-1, sTNFR1, RANTES, VEGF, IL-6, IL-10, TNF and Eotaxin) was measured in the plasma of 100 control subjects and 100 TB patients, at diagnosis (treatment na€ ıve) and over the course of treatment (1-, 2-and 6month intervals). The diagnostic performance of the nine proteins alone, and with the miRNA, was assessed. Results. Six proteins were significantly up-regulated in the plasma of TB patients at diagnosis compared to controls. Receiver operator characteristic curve analysis demonstrated that IP-10 with an AUC = 0.874, sensitivity of 75% and specificity of 87% was the best single biomarker candidate to distinguish TB patients from controls. IP-10 and IL-6 levels fell significantly within one month of commencing treatment and may have potential as indicators of a positive response to therapy. The combined protein and miRNA panel gave an AUC of 1.00. A smaller panel of only five analytes (IP-10, miR-29a, miR-146a, miR-99b and miR-221) showed an AUC = 0.995, sensitivity of 96% and specificity of 97%. Conclusions. A novel combination of miRNA and proteins significantly improves the sensitivity and specificity as a biosignature over single biomarker candidates and may be useful for the development of a nonsputum test to aid the diagnosis of active TB disease.
Identification of Serum microRNA Biomarkers for Tuberculosis Using RNA-seq
PLoS ONE, 2014
Tuberculosis (TB) remains a significant human health issue. More effective biomarkers for use in tuberculosis prevention, diagnosis, and treatment, including markers that can discriminate between healthy individuals and those with latent infection, are urgently needed. To identify a set of such markers, we used Solexa sequencing to examine microRNA expression in the serum of patients with active disease, healthy individuals with latent TB, and those with or without prior BCG inoculation. We identified 24 microRNAs that are up-regulated (2.85-1285.93 fold) and 6 microRNAs that are downregulated (0.003-0.11 fold) (P,0.05) in patients with active TB relative to the three groups of healthy controls. In addition, 75 microRNAs were up-regulated (2.05-2454.58 fold) and 11 were down-regulated (0.001-0.42 fold) (P,0.05) in latent-TB infected individuals relative to BCG-inoculated individuals. Of interest, 134 microRNAs were differentially-expressed in BCGinoculated relative to un-inoculated individuals (18 up-regulated 2.9-499.29 fold, 116 down-regulated 0.0002-0.5 fold), providing insights into the effects of BCG inoculation at the microRNA level. Target prediction of differentially-expressed microRNAs by microRNA-Gene Network analysis and analysis of pathways affected suggest that regulation of the host immune system by microRNAs is likely to be one of the main factors in the pathogenesis of tuberculosis. qRT-PCR validation indicated that hsa-miR-196b and hsa-miR-376c have potential as markers for active TB disease. The microRNA differentialexpression profiles generated in this study provide a good foundation for the development of markers for TB diagnosis, and for investigations on the role of microRNAs in BCG-inoculated and latent-infected individuals.
Host and MTB genome encoded miRNA markers for diagnosis of tuberculosis
Tuberculosis, 2019
MicroRNAs (miRNAs) are a class of noncoding RNA molecules which are involved in various cellular and physiological processes. Previously, studies have identified several miRNAs that are potential diagnostic biomarkers for various infectious diseases including tuberculosis. We have performed small RNA sequencing using the Ion Torrent PGM platform in extra pulmonary tuberculosis (EPTB) subject's serum samples to identify circulating miRNAs during mycobacterium tuberculosis (MTB) infection. Our analysis identified 20 circulating miRNAs upregulated and 5 miRNAs downregulated during MTB infection in patient's serum. In addition, we have identified 6 MTB genome encoded miRNAs upregulated in EPTB patient's serum samples. Taqman based qRT-PCR analysis of host-genome encoded (hsa-miR-146a-5p and hsa-miR-125b-5p) and MTB genome encoded (MTB-miR5) miRNAs showed increased expression in a cohort of 52 healthy, pulmonary tuberculosis (PTB) and extra pulmonary tuberculosis (EPTB) patients serum samples. Our study identified for the first time a panel of host and MTB genome specific differentially expressed circulating miRNAs in serum samples of an Indian patient cohort with tuberculosis infection with a potential as a non-invasive diagnostic biomarker for tuberculosis infection.