Competing endogenous RNAs (ceRNAs) orchestrate a gene regulatory network in the Aedes aegypti midgut in response to blood feeding

Aedes aegypti, a globally widespread mosquito, is a key public health threat due to its ability to transmit multiple deadly arboviruses. The midgut is crucial for the survival, reproduction, and disease transmission of mosquitoes. Competing endogenous RNAs (ceRNAs) regulate gene expression by competing for miRNA response elements (MREs), influencing processes like immunity, growth, and disease. While numerous studies have investigated miRNAs and lncRNAs in mosquitoes, the relationship between ceRNAs and nutrient uptake in the mosquito midgut remains largely unexplored. In this study, we employed whole transcriptome sequencing to identify differentially expressed (DE) miRNAs, mRNAs, lncRNAs, and circRNAs in the midgut of blood-fed Ae. aegypti mosquitoes. We identified 22 DEmiRNAs, 4226 DEmRNAs, 1238 DElncRNAs, and 35 DEcircRNAs, and developed regulatory networks for DE lncRNA/miRNA/mRNA and DE circRNA/miRNA/mRNA interactions. In these networks, DEmRNAs, DEmiRNA targets, and DEcircRNA host genes are enriched in processes like DNA integration, DNA metabolism, membrane lumen sealing, and RNA catalytic activity. KEGG analysis shows these genes are mainly involved in pathways such as mucin-type O-glycan biosynthesis and pantothenic acid and coenzyme A biosynthesis. Notably, miR-305-5p, miR-275-3p, miR-11-5p, miR-33, and miR-34-3p are key components of the ceRNA network, interacting with DElncRNAs, DEcircRNAs, and DEmRNAs. In conclusion, this study identified lncRNAs, mRNAs, miRNAs, and circRNAs in the midgut of Ae. aegypti that respond significantly to blood stimulation, suggesting their key roles in nutrient absorption regulation. These findings enhance our understanding of the molecular mechanisms of nutrient absorption and transformation in Ae. aegypti by clarifying RNA interactions.