The characterization of extracellular vesicles-derived microRNAs in Thai malaria patients

Abstract

Background: Extracellular vesicles (EVs) have been broadly studied in malaria for nearly a decade. These vesicles carry various functional biomolecules including RNA families such as microRNAs (miRNA). These EVs-derived microR-NAs have numerous roles in host-parasite interactions and are considered promising biomarkers for disease severity. However, this field lacks clinical studies of malaria-infected samples. In this study, EV specific miRNAs were isolated from the plasma of patients from Thailand infected with Plasmodium vivax and Plasmodium falciparum. In addition, it is postulated that these miRNAs were differentially expressed in these groups of patients and had a role in disease onset through the regulation of specific target genes. Methods: EVs were purified from the plasma of Thai P. vivax-infected patients (n = 19), P. falciparum-infected patients (n = 18) and uninfected individuals (n = 20). EV-derived miRNAs were then prepared and abundance of hsa-miR-15b-5p, hsa-miR-16-5p, hsa-let-7a-5p and hsa-miR-150-5p was assessed in these samples. Quantitative polymerase chain reaction was performed, and relative expression of each miRNA was calculated using hsa-miR-451a as endogenous control. Then, the targets of up-regulated miRNAs and relevant pathways were predicted by using bioinformatics. Receiver Operating Characteristic with Area under the Curve (AUC) was then calculated to assess their diagnostic potential. Results: The relative expression of hsa-miR-150-5p and hsa-miR-15b-5p was higher in P. vivax-infected patients compared to uninfected individuals, but hsa-let-7a-5p was up-regulated in both P. vivax-infected patients and P. falciparum-infected patients. Bioinformatic analysis revealed that these miRNAs might regulate genes involved in the malaria pathway including the adherens junction and the transforming growth factor-β pathways. All up-regulated miRNAs could potentially be used as disease biomarkers as determined by AUC; however, the sensitivity and specificity require further investigation.

Extracellular vesicles in malaria: an agglomeration of two decades of research

“…Protectively packaged into EVs, miRNAs are now known to play vital roles in protozoan and other infectious diseases [ 63 , 64 ]. Plasmodium infection evidently alters miRNA expression, as distinct plasma EV-miRNA profiles in murine malaria models [ 58 ] and human malaria [ 60 ] have been identified. In EVs from P. berghei ECM, the expression of miR-146a and miR-193b was found to be significantly dysregulated compared to EVs in Plasmodium yoelii non-CM and non-infected mice; while miR-146a was markedly upregulated in EVs, miR-193b was downregulated [ 58 ].…”

“…In EVs from P. berghei ECM, the expression of miR-146a and miR-193b was found to be significantly dysregulated compared to EVs in Plasmodium yoelii non-CM and non-infected mice; while miR-146a was markedly upregulated in EVs, miR-193b was downregulated [ 58 ]. In humans, when compared with uninfected individuals, the miRNA hsa-let-7a-5p was upregulated in EVs from patients with falciparum and vivax malaria, while miRNAs hsa-miR-150-5p and hsa-miR-15b-5p were both upregulated in vivax malaria alone [ 60 ]. These and other miRNAs have already been implicated in other neurological diseases and were predicted to be of importance in pathways relevant to malaria, such as EV biogenesis, inflammation, cytoadhesion, [ 58 ], adherens junction and transforming growth factor (TGF)-β pathways [ 60 ].…”

Drug repurposing for coronavirus (SARS-CoV-2) based on gene co-expression network analysis

“…In Zofia Wicik et al 63 showed that this miRNA could regulate ACE2 networks. Moreover, this miRNA can link the pathogenesis of HIV-1 and malaria 64 – 66 . Similarly, Jianghong Wei et al 67 found that overexpression of miR-16 inhibited the growth and metastasis of the DMS-53 lung cancer cells.…”

ACE2 interaction networks in COVID-19: a physiological framework for prediction of outcome in patients with cardiovascular risk factors

“…hsa-miR-16-5p was found to affect a phenotypic change of T cells, modulate inflammatory signalling and cytokines including IL-1β, IL-6 and TNF-α, NF-κB mTOR-related pathways and genes [103,104]. Additionally, MiR-16-5p has been linked with the pathogenesis of several infectious diseases such as HIV-1 infection and malaria [105–107]. It is worth mentioning that miR-16-5p as a plasma diagnostic biomarker is able to distinguish severe and mild viral infections [108] and early HIV-1 infection from healthy individuals [106,109].…”