Abstract

Ricin toxin (RT) is one of the most lethal toxins derived from the seed of castor beans. In addition to its main toxic mechanism of inhibiting the synthesis of cellular proteins, RT can induce the production of inflammatory cytokines. MicroRNAs (miRNAs) play a key role in regulating both innate and adaptive immunity. To elucidate the regulation of miRNAs in RT-induced inflammation injury, the RNA high-throughput sequencing (RNA-Seq) technology was used to analyze the expression profile of miRNAs and mRNAs in RT-treated RAW264.7 cells. Results showed that a total of 323 mRNAs and 19 miRNAs differentially expressed after RT treated. Meanwhile, 713 miRNA-mRNA interaction pairs were identified by bioinformatics analysis. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that those interaction pairs were mainly involved in JAK-STAT, T cell receptor, and MAPK signaling pathways. Moreover, we further predicted and determined the targeting relationship between miR-155-3p and GAB2 through TargetScan and dual-luciferase reporter assay. Mechanically, overexpression of miR-155-3p can reduce the secretion of TNF-α in RAW264.7 cells, revealing a possible mechanism of miR-155-3p regulating RT-induced inflammatory injury. This study provides a new perspective for clarifying the mechanism of RT-induced inflammatory injury and reveals the potential role of miRNAs in innate immune regulation.

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