Dataset Information

Identification of Circulating miR-22-3p and miR-93-5p as Stable Endogenous Control in Tuberculosis Study.

ABSTRACT: The diagnosis and prognosis of tuberculosis remains challenging and necessitates the development of a new test that can accurately diagnose and monitor treatment responses. In this regard, miRNA is becoming a potential diagnostic and prognostic biomarker which differentiates treatment respondents from non-respondents for various non-infectious and infectious diseases, including tuberculosis. The concentration of miRNAs varies based on cell type, disease, and site of infection, implicating that selection of an optimal reference gene is crucial, and determines the quantification of transcript level and biological interpretation of the data. Thus, the study evaluated the stability and expression level of five candidate miRNAs (let-7i-5p, let-7a-5p, miRNA-16-5p, miRNA-22-3p and miRNA-93-5p), including U6 Small Nuclear RNA (RNU6B) to normalize circulating miRNAs in the plasma of 68 participants (26 healthy controls, 23 latent, and 19 pulmonary tuberculosis infected) recruited from four health centers and three hospitals in Addis Ababa, Ethiopia. The expression levels of miRNAs isolated from plasma of culture confirmed newly diagnosed pulmonary tuberculosis patients were compared with latently infected and non-infected healthy controls. The qPCR data were analyzed using four independent statistical tools: Best Keeper, Genorm, Normfinder and comparative delta-Ct methods, and the data showed that miRNA-22-3p and miRNA-93-5p were suitable plasma reference miRNAs in a tuberculosis study.

SUBMITTER: Korma W

PROVIDER: S-EPMC7690830 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Identification of Circulating miR-22-3p and miR-93-5p as Stable Endogenous Control in Tuberculosis Study.

Korma Workneh W Mihret Adane A Tarekegn Azeb A Chang Yunhee Y Hwang Dasom D Tessema Tesfaye Sisay TS Lee Hyeyoung H

Diagnostics (Basel, Switzerland) 20201023 11

The diagnosis and prognosis of tuberculosis remains challenging and necessitates the development of a new test that can accurately diagnose and monitor treatment responses. In this regard, miRNA is becoming a potential diagnostic and prognostic biomarker which differentiates treatment respondents from non-respondents for various non-infectious and infectious diseases, including tuberculosis. The concentration of miRNAs varies based on cell type, disease, and site of infection, implicating that s ...[more]

PMID: 33114169

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Project description:Low-dose computed tomography (LDCT) Non-Small Cell Lung (NSCLC) screening is associated with high false-positive rates, leading to unnecessary expensive and invasive follow ups. There is a need for minimally invasive approaches to improve the accuracy of NSCLC diagnosis. In addition, NSCLC patients harboring sensitizing mutations in epidermal growth factor receptor EGFR (T790M, L578R) are treated with Osimertinib, a potent tyrosine kinase inhibitor (TKI). However, nearly all patients develop TKI resistance. The underlying mechanisms are not fully understood. Plasma extracellular vesicle (EV) and circulating microRNA (miRNA) have been proposed as biomarkers for cancer screening and to inform treatment decisions. However, the identification of highly sensitive and broadly predictive core miRNA signatures remains a challenge. Also, how these systemic and diverse miRNAs impact cancer drug response is not well understood. Using an integrative approach, we examined plasma EV and circulating miRNA isolated from NSCLC patients versus screening controls with a similar risk profile. We found that combining EV (Hsa-miR-184, Let-7b-5p) and circulating (Hsa-miR-22-3p) miRNAs abundance robustly discriminates between NSCLC patients and high-risk cancer-free controls. Further, we found that Hsa-miR-22-3p, Hsa-miR-184, and Let-7b-5p functionally converge on WNT/βcatenin and mTOR/AKT signaling axes, known cancer therapy resistance signals. Targeting Hsa-miR-22-3p and Hsa-miR-184 desensitized EGFR-mutated (T790M, L578R) NSCLC cells to Osimertinib. These findings suggest that the expression levels of circulating hsa-miR-22-3p combined with EV hsa-miR-184 and Let-7b-5p levels potentially define a core biomarker signature for improving the accuracy of NSCLC diagnosis. Importantly, these biomarkers have the potential to enable prospective identification of patients who are at risk of responding poorly to Osimertinib alone but likely to benefit from Osimertinib/AKT blockade combination treatments.

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Project description:Purpose:Metabolic syndrome (MetS) is associated with chronic stress. miR-18a-5p and miR-22-3p are two miRNAs which can target the glucocorticoid receptor. This study looked at the changes in metabolic parameters and the predictive value of the peripheral blood mononuclear cells (PBMCs) to stress-associated miRNA ratios as new indicators in subjects with and without MetS in southern China. Patients and Methods. There were 81 participants (39 with MetS and 42 without MetS) in this cross-sectional study. The potential miRNAs were filtrated in the GEO database. The expression of miR-18a-5p and miR-22-3p in PBMCs was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The risk of miRNA and PBMCs to stress-associated miRNA ratios contributing to the presence of MetS was estimated by univariate and multivariate logistic regression models. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Results:MetS was positively correlated with cortisol, IL-6, lymphocyte to miR-18a-5p ratio (LT18R), lymphocyte to miR-22-3p ratio (LT22R), monocyte to miR-18a-5p ratio (MT18R), monocyte to miR-22-3p ratio (MT22R), PBMCs to miR-18a-5p ratio (PT18R), and PBMCs to miR-22-3p ratio (PT22R) and negatively associated with the expression levels of miR-18a-5p and miR-22-3p (P < 0.05). In addition, PT18R (odds ratio: 0.894; 95% CI: 0.823-0.966; P < 0.001) and PT22R (odds ratio: 0.809; 95% CI: 0.717-0.900; P < 0.001) were independent predictors of MetS, respectively. A receiver operating characteristic (ROC) curve analysis was performed to assess the value of the PT18R-PT22R (PMR) panel (odds ratio: 0.905; 95% CI: 0.838-0.971; P < 0.001) for predicting MetS. The area under the curve yielded a cut-off value of 0.608, with sensitivity of 74.4% and specificity of 95.2% (P < 0.001). Conclusion:In summary, miR-18a-5p and miR-22-3p in PBMCs may be important biomarkers of stress reaction and may play a role in vulnerability to MetS. Besides, the inflammatory cells to the two miRNA ratios demonstrated high accuracy in the diagnosis of MetS.

Dataset Information

Identification of Circulating miR-22-3p and miR-93-5p as Stable Endogenous Control in Tuberculosis Study.

Publications

Identification of Circulating miR-22-3p and miR-93-5p as Stable Endogenous Control in Tuberculosis Study.

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