Plasma microRNA profiling for malaria disease: association with severity and P. falciparum biomass (original) (raw)
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Circulating microRNAs in malaria infection: bench to bedside
Malaria Journal, 2017
Severe malaria has a poor prognosis with a morbidity rate of 80% in tropical areas. The early parasite detection is one of the effective means to prevent severe malaria of which specific treatment strategies are limited. Many clinical characteristics and laboratory testings have been used for the early diagnosis and prediction of severe disease. However, a few of these factors could be applied to clinical practice. MicroRNAs (miRNAs) were demonstrated as useful biomarkers in many diseases such as malignant diseases and cardiovascular diseases. Recently it was found that plasma miR-451 and miR-16 were downregulated in malaria infection at parasitic stages or with multi-organ failure involvement. MiR-125b,-27a,-23a,-150, 17-92 and-24 are deregulated in malaria patients with multiple organ failures. Here, the current findings of miRNAs were reviewed in relation to clinical severity of malaria infection and emphasized that miRNAs are potential biomarkers for severe malaria infection.
Tying malaria and microRNAs: from the biology to future diagnostic perspectives
Malaria Journal, 2016
Symptoms caused by bacterial, viral and malarial infections usually overlap and aetiologic diagnosis is difficult. Patient management in low-resource countries with limited laboratory services has been based predominantly on clinical evaluation and syndromic approaches. However, such clinical assessment has limited accuracy both for identifying the likely aetiological cause and for the early recognition of patients who will progress to serious or fatal disease. Plasma-detectable biomarkers that rapidly and accurately diagnose severe infectious diseases could reduce morbidity and decrease the unnecessary use of usually scarce therapeutic drugs. The discovery of microRNAs (miRNAs) has opened exciting new avenues to identify blood biomarkers of organ-specific injury. This review assesses current knowledge on the relationship between malaria disease and miRNAs, and evaluates how future research might lead to the use of these small molecules for identifying patients with severe malaria disease and facilitate treatment decisions.
Dichotomous miR expression and immune responses following primary blood-stage malaria
JCI insight, 2017
Clinical responses to infection or vaccination and the development of effective immunity are characterized in humans by a marked interindividual variability. To gain an insight into the factors affecting this variability, we used a controlled human infection system to study early immune events following primary infection of healthy human volunteers with blood-stage Plasmodium falciparum malaria. By day 4 of infection, a dichotomous pattern of high or low expression of a defined set of microRNAs (miRs) emerged in volunteers that correlated with variation in parasite growth rate. Moreover, high-miR responders had higher numbers of activated CD4+ T cells, and developed significantly enhanced antimalarial antibody responses. Notably, a set of 17 miRs was identified in the whole blood of low-miR responders prior to infection that differentiated them from high-miR responders. These data implicate preexisting host factors as major determinants in the ability to effectively respond to prima...
Erythrocyte miRNA-92a-3p interactions with PfEMP1 as determinants of clinical malaria
Functional & Integrative Genomics
Based on the recently added high throughput analysis data on small noncoding RNAs in modulating disease pathophysiology of malaria, we performed an integrative computational analysis for exploring the role of human-host erythrocytic microRNAs (miRNAs) and their influence on parasite survival and host homeostasis. An in silico analysis was performed on transcriptomic datasets accessed from PlasmoDB and Gene Expression Omnibus (GEO) repositories analyzed using miRanda, miRTarBase, mirDIP, and miRDB to identify the candidate miRNAs that were further subjected to network analysis using MCODE and DAVID. This was followed by immune infiltration analysis and screening for RNA degradation mechanisms. Seven erythrocytic miRNAs, miR-451a, miR-92a-3p, miR-16-5p, miR-142-3p, miR-15b-5p, miR-19b-3p, and miR-223-3p showed favourable interactions with parasite genes expressed during blood stage infection. The miR-92a-3p that targeted the virulence gene PfEMP1 showed drastic reduction during infect...
MiRNA: Biological Regulator in Host-Parasite Interaction during Malaria Infection
International Journal of Environmental Research and Public Health, 2022
Malaria is a severe life-threatening disease caused by the bites of parasite-infected female Anopheles mosquitoes. It remains a significant problem for the most vulnerable children and women. Recent research has helped establish the relationship between microRNAs (miRNAs) and many other diseases. MiRNAs are the class of small non-coding RNAs consisting of 18–23 nucleotides in length that are evolutionarily conserved and regulate gene expression at a post-transcriptional level and play a significant role in various molecular mechanisms such as cell survival, cell proliferation, and differentiation. MiRNAs can help detect malaria infection as the malaria parasite could alter the miRNA expression of the host. These alterations can be diagnosed by the molecular diagnostic tool that can indicate disease. We summarize the current understanding of miRNA during malaria infection. miRNAs can also be used as biomarkers, and initial research has unearthed their potential in diagnosing and mana...
International Journal of Gastroenterology Hepatology and Endoscopy
Plasmodium falciparum infection causes paroxysmal fever that is triggered by strong pro-inflammatory responses involving pyrogenic cytokines such as interleukin (IL)-1β and tumor necrosis factor alpha (TNF-α). Although inflammatory responses, including interferon gamma (IFN-γ), IL-12, IL-1β, IL-2, and TNF-α, play important roles that facilitate parasite clearance, circulating high levels of these cytokines have been associated with malaria immunopathology (Ademolue et al., 2017). The miRNAs and malaria is a dynamic interaction still incomplete understood. Therefore, authors come up with selected genes such as CD36, IFN-γ, toll-like receptor 4 (TLR4) and proline rich 15 (PRR15) consider as candidate genes that expressed become miRNAs and can be served as potential biomarkers in malaria infection. Micro ribonucleic acids (miRNAs) are a class of small non-coding endogenous RNA molecules (Rangel G et al., 2019) that regulate a wide range of biological processes by post-transcriptionally regulating
Downregulation of plasma miR-451 and miR-16 in Plasmodium vivax infection
Experimental Parasitology, 2015
The objective is to develop the new biomarker for malaria infections. • This is the first observation of plasma microRNAs in malaria. • Plasma miR-451 and miR-16 were downregulated in Plasmodium vivax infection. • We discuss the usefulness of plasma microRNAs as the biomarkers for malaria infections.
ExRNA, 2021
Background: Plasmodium falciparum (P. falciparum) is one of the deadliest species responsible for the major deaths related to malaria. Recently emerging research has focused on small noncoding RNAs especially mature microRNAs (miRNAs) (19-25 nts) which play regulatory role chiefly by targeting mRNAs' cleavage or translational repression. During infection, parasitic Plasmodium invades and takes command of the host cell for its survival and develops into its various life stages. Seeing that host, miRNAs considered as chief regulators of various physiological functions of the cell itself. During erythrocytic stages, possible interactions between the erythrocytic miRNAs and Plasmodium mRNAs may affect parasite biology and its survival inside the host cell. It has been also reported that during erythrocytic stages of P. falciparum, erythrocytic miRNAs may translocate into the parasite phosphorous vacuole, some of them may forming a chimera with Plasmodium mRNAs to get involved in post transcriptional regulation. Methods: In this study, one of the most abundant human erythrocytic miR-451a retrieved from miRbase and targeted on P. falciparum 3D7 transcriptome to find out the target genes and followed by annotation studies performed of targeted genes. Results: We identified crucial gene targets of P. falciparum using PSRNA target tool. Functional annotation of targeted genes and their protein products help us to understand the possible protein-protein interaction during the course of infection as well as analysis of their functions at molecular/cellular/biological level shows the significant contribution from the cytoskeletal genes which codes for the proteins like Plasmodium falciparum 3D7 erythrocyte membrane protein 1 (PfEMP1), rifin, etc. which are involved in the host membrane modifications. Conclusions: Computational approach to elucidate the erythrocytic microRNA (miRNA) targeted genes and their functional annotation studies will help to understand the possible interactions and miRNA regulatory network in malaria.