miRNAs and Leukotrienes in Respiratory Syncytial Virus Infection

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate posttranscription by binding to 3'-untranslated regions of target mRNAs. Recent functional studies have elucidated mechanisms that miRNAs regulate leukotriene synthesis by perturbing arachidonic acid metabolism. Both microarrays and high-throughput sequencing revealed distinct differential expression of miRNAs in children with respiratory syncytial virus (RSV) infection compared with healthy controls. Abnormal miRNA expression may contribute to higher leukotriene levels, which is associated with airway hyperreactivity. Targeting miRNAs may benefit to restore the homeostasis of inflammatory reaction and provide new strategies to alleviate airway hyperreactivity induced by RSV. In this article, we provide an overview of the current knowledge about miRNAs modulating leukotrienes through regulation of arachidonic acid metabolism with a special focus on miRNAs aberrantly expressed in children with RSV infection.

Keywords: arachidonic acid; children; leukotriene; microRNA; respiratory syncytial virus.

Figure 1

miRNAs were validated to modulate the metabolism of arachidonic acid (AA). In airway epithelial cells, RSVs are recognized by PAMPs such as TLRs, which subsequently activate signal pathways like NF-κB and affect the expression profile of miRNAs. MiRNAs regulate leukotriene synthesis by modulating AA metabolism, which mainly includes the LOX pathway and COX pathway. Thereinto, miR-219-2 can inhibit several enzymes such as cPLA2, 5-LOX, and LTA₄H. Some miRNAs have been confirmed to inhibit the expression of 5-LOX, such as let-7, miR-19a, and miR-125. In addition, miR-146a, miR-135a, and miR-199 can regulate 5-LOX enzyme activity by downregulating FLAP; let-7 and miR-21 by downregulating p38 MAPK. Interference with these miRNAs may contribute to the consistently overexpressed leukotrienes. MiRNAs such as miR-16, miR-26, miR-30a, miR-143, and miR-146a may lead to the conversion of more AA to leukotriene by inhibiting the COX pathway. Besides, overexpression of miRNAs like miR-101 and miR-106a can suppress 12-LOX/15-LOX, which could disrupt the balance between pro-inflammatory and inflammation-resolving mediators. Among these miRNAs, let-7, miR-16-5p, miR-19a, miR-21, miR-26b, miR-30a-5p, miR-125a, miR-143, and miR-146a have been found abnormal expression in RSV infection.