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Journal ArticleDOI

MicroRNAs and Malaria - A Dynamic Interaction Still Incompletely Understood.

01 Mar 2015-Journal of neuroinfectious diseases (OMICS International)-Vol. 6, Iss: 1, pp 165

AbstractMalaria is a mosquito-borne infectious disease caused by parasitic protozoa of the genus Plasmodium. It remains a major problem affecting humans today, especially children. However, the pathogenesis of malaria, especially severe malaria, remains incompletely understood, hindering our ability to treat this disease. Of recent interest is the role that small, non-coding RNAs play in the progression, pathogenesis of, and resistance to, malaria. Independent studies have now revealed the presence of microRNA (miRNA) in the malaria parasite, vector, and host, though these studies are relatively few. Here, we review these studies, focusing on the roles specific miRNA have in the disease, and how they may be harnessed for therapeutic purposes.

Topics: Malaria (55%)

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Journal ArticleDOI
Song Jiang1, Xin Li1, Xuhai Wang1, Qian Ban2, Wenqiao Hui1, Bin Jia1 
01 Jan 2016-Parasite
TL;DR: To identify microRNA controlling resistance to CE in the early stage of infection, microRNA profiling was conducted in the intestinal tissue of sheep with resistant and non-resistant MHC haplotypes after peroral infection with E. granulosus.
Abstract: Cystic echinococcosis (CE), caused by infection with the larval stage of the cestode Echinococcus granulosus , is a chronic zoonosis, to which sheep are highly susceptible. Previously, we found that Kazakh sheep with different MHC haplotypes differed in CE infection. Sheep with haplotype MHCMva Ibc-Sac IIab-Hin 1Iab were resistant to CE infection, while their counterparts without this haplotype were not. MicroRNAs (miRNAs), a class of small non-coding RNAs, are key regulators of gene expression at the post-transcriptional level and play essential roles in fundamental biological processes such as development and metabolism. To identify microRNA controlling resistance to CE in the early stage of infection, microRNA profiling was conducted in the intestinal tissue of sheep with resistant and non-resistant MHC haplotypes after peroral infection with E. granulosus eggs. A total of 351 known and 186 novel miRNAs were detected in the resistant group, against 353 known and 129 novel miRNAs in the non-resistant group. Among these miRNAs, 83 known miRNAs were significantly differentially expressed, including 75 up-regulated and 8 down-regulated miRNAs. Among these known microRNAs, miR-21-3p, miR-542-5p, miR-671, miR-134-5p, miR-26b, and miR-27a showed a significantly higher expression in CE-resistant sheep compared to the CE-non-resistant library, with the FC > 3. Functional analysis showed that they were NF-kB pathway-responsive miRNAs, which are involved in the inflammation process. The results suggest that these microRNAs may play important roles in the response of intestinal tissue to E. granulosus .

23 citations


Journal ArticleDOI
TL;DR: It is reasoned that culture conditions should be re-established as a primary consideration in in vitro malaria experimentation.
Abstract: The advent of Plasmodium falciparum (Pf) in vitro culturing opened the door for malaria research, yielding dramatic advancements in our understanding of the parasite. However, fundamental foundations taken for granted in our research endeavors can unknowingly be an Achilles heel, resulting in potential misdirection. In relation to malaria research, this could be our nonquestioning acceptance of routine in vitro culture of Pf. There is nothing routine or straightforward regarding the dynamic and intimate relationship between the parasite and the in vitro environment. Here, we discuss recent studies demonstrating the impact that slight variations in in vitro Pf culture parameters can have on scientific conclusions. We reason that culture conditions should be re-established as a primary consideration in in vitro malaria experimentation.

20 citations


Journal ArticleDOI
TL;DR: The data implies that, at least in the mouse model, miRNA may play a regulatory role in CM pathogenesis, and suggests that these miRNA, through their regulation of downstream targets, may be vitally involved in the neurological syndrome.
Abstract: Cerebral malaria (CM) is the most severe manifestation of infection with Plasmodium, however its pathogenesis is still not completely understood. microRNA (miRNA) have been an area of focus in infectious disease research, due to their ability to affect normal biological processes, and have been shown to play roles in various viral, bacterial and parasitic infections, including malaria. The expression of miRNA was studied following infection of CBA mice with either Plasmodium berghei ANKA (causing CM), or Plasmodium yoelii (causing severe but non-cerebral malaria (NCM)). Using microarray analysis, miRNA expression was compared in the brains of non-infected (NI), NCM and CM mice. Six miRNA were significantly dysregulated between NCM and CM mice, and four of these, miR-19a-3p, miR-19b-3p, miR-142-3p and miR-223-3p, were further validated by qPCR assays. These miRNA are significantly involved in several pathways relevant to CM, including the TGF-β and endocytosis pathways. Dysregulation of these miRNA during CM specifically compared with NCM suggests that these miRNA, through their regulation of downstream targets, may be vitally involved in the neurological syndrome. Our data implies that, at least in the mouse model, miRNA may play a regulatory role in CM pathogenesis.

17 citations


Journal ArticleDOI
TL;DR: The change in abundance of miRNA was studied following infection of CBA mice with Plasmodium berghei ANKA strain, and Plas modium yoelii, which causes severe malaria without cerebral complications, termed non-CM, suggesting that, in the mouse model at least, miRNA may have a regulatory role in the pathogenesis of severe malaria.
Abstract: Cerebral malaria (CM) is a fatal complication of Plasmodium infection, mostly affecting children under the age of five in the sub-Saharan African region. CM pathogenesis remains incompletely understood, although sequestered infected red blood cells, inflammatory cells aggregating in the cerebral blood vessels, and the microvesicles (MV) that they release in the circulation, have been implicated. Plasma MV numbers increase in CM patients and in the murine model, where blocking their release, genetically or pharmacologically, protects against brain pathology, suggesting a role of MV in CM neuropathogenesis. In this work, the microRNA (miRNA) cargo of MV is defined for the first time during experimental CM with the overarching hypothesis that this characterization could help understand CM pathogenesis. The change in abundance of miRNA was studied following infection of CBA mice with Plasmodium berghei ANKA strain (causing experimental CM), and Plasmodium yoelii, which causes severe malaria without cerebral complications, termed non-CM (NCM). miRNA expression was analyzed using microarrays to compare MV from healthy (NI) and CM mice, yielding several miRNA of interest. The differential expression profiles of these selected miRNA (miR-146a, miR-150, miR-193b, miR-205, miR-215, miR-467a, and miR-486) were analyzed in mouse MV, MV-free plasma, and brain tissue by quantitative reverse transcription PCR (RT-qPCR). Two miRNA—miR-146a and miR-193b—were confirmed as differentially abundant in MV from CM mice, compared with NCM and NI mice. These miRNA have been shown to play various roles in inflammation, and their dysregulation during CM may be critical for triggering the neurological syndrome via regulation of their potential downstream targets. These data suggest that, in the mouse model at least, miRNA may have a regulatory role in the pathogenesis of severe malaria.

15 citations


Journal ArticleDOI
TL;DR: In silico analysis of the common targets of up-regulated miRNAs revealed UBA52 and hsa-miR-7977 as majorly regulated hubs in the PPI and mRNA–miRNA networks, suggesting their putative role in complicated P. vivax malaria.
Abstract: In the recent years Plasmodium vivax has been reported to cause severe infections associated with mortality. Clinical evaluation has limited accuracy for the early identification of the patients progressing towards the fatal condition. Researchers have tried to identify the serum and the plasma-based indicators of the severe malaria. Discovery of MicroRNA (miRNA) has opened up an era of identification of early biomarkers for various infectious and non-infectious diseases. MicroRNAs (miRNA) are the small non-coding RNA molecules of length 19–24 nts and are responsible for the regulation of the majority of human gene expressions at post transcriptional level. We identified the differentially expressed miRNAs by microarray and validated the selected miRNAs by qRT-PCR. We assessed the diagnostic potential of these up-regulated miRNAs for complicated P. vivax malaria. Futher, the bioinformtic analysis was performed to construct protein–protein and mRNA–miRNA networks to identify highly regulated miRNA. In the present study, utility of miRNA as potential biomarker of complicated P. vivax malaria was explored. A total of 276 miRNAs were found to be differentially expressed by miRNA microarray and out of which 5 miRNAs (hsa-miR-7977, hsa-miR-28-3p, hsa-miR-378-5p, hsa-miR-194-5p and hsa-miR-3667-5p) were found to be significantly up-regulated in complicated P. vivax malaria patients using qRT-PCR. The diagnostic potential of these 5 miRNAs were found to be significant with sensitivity and specificity of 60–71% and 69–81% respectively and area under curve (AUC) of 0.7 (p < 0.05). Moreover, in silico analysis of the common targets of up-regulated miRNAs revealed UBA52 and hsa-miR-7977 as majorly regulated hubs in the PPI and mRNA–miRNA networks, suggesting their putative role in complicated P. vivax malaria. miR-7977 might act as a potential biomarker for differentiating complicated P. vivax malaria from uncomplicated type. The elevated levels of miR-7977 may have a role to play in the disease pathology through UBA52 or TGF-beta signalling pathway.

15 citations


References
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Journal ArticleDOI
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785 citations


Journal ArticleDOI
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730 citations


Journal ArticleDOI
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717 citations


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