Differentially expressed microRNAs in experimental cerebral malaria and their involvement in endocytosis, adherens junctions, FoxO and TGF-β signalling pathways

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.

LncRNA-NEAT1 from the competing endogenous RNA network promotes cardioprotective efficacy of mesenchymal stem cell-derived exosomes induced by macrophage migration inhibitory factor via the miR-142-3p/FOXO1 signaling pathway

“…The FOXO family of transcription factors serves as the integration of growth factor signaling, oxidative stress, and inflammation [20], by regulating the expression of several antioxidant enzyme genes, including SOD [21]. MiR-142-3p has also been suggested to regulate FOXO function under oxidative stress conditions [22]. FOXO transcription factors are crucial to heart homeostasis [23], and FOXO1 critically determines cardiomyocyte apoptosis, left ventricular remodeling, and ischemic oxidative stress [24,25].…”

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

“…Also, the overexpression of miR-142-3p repressed the expression of VE-Cadherin and impaired vascular integrity in zebra sh [58]. Similarly, in ECM, the authors postulated the roles of overexpressed miR-19a-3p and miR-19b-5p in this pathway as well [40]. Knowing the roles of miRNAs in the context of malaria particularly cerebral malaria pathogenesis is paramount as it might lead to the development of an adjunctive therapy.…”

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

“…In order to provide knowledge about dysregulated miRNAs of interest, target prediction was up-regulated of miR-19a-3p and miR-19b-5p were associated with TGF-β pathway [43]. However, our study did not include these miRNAs.…”

“…In other studies, expression of miRNAs in heart and brain tissues from mice with cerebral malaria were shown to be dysregulated when compared to non-cerebral malaria [42,43].…”