MicroRNA-221-5p Promotes Ricin Toxin-induced Inflammation via PI3K/Akt signaling pathway by targeting COL4a5. (June 2022)

• Record Type: Journal Article
• Authors: Zhao, Na; Yu, Haotian; Xi, Yanli; Dong, Mingxin; Wang, Yan; Sun, Chengbiao; Zhang, Jianxu; Xu, Na; Liu, Wensen
• Is Part Of: Toxicon. Volume 212(2022)
• Page Start: 11
• Page End: 18
• Publication Date: 2022-06
• Subjects: Ricin toxin -- miRNAs -- Inflammation -- PI3K/Akt -- COL4a5; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2022.03.010
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: Ricin toxin (RT) is one of the most lethal type II ribosome-inactivating proteins (RIP), and is classified as a potential bioterror agent due to its severe cytotoxicity and high availability. The toxicity of RT is dependent on both dose and route of exposure. Increasing evidence demonstrates that sub-lethal RT induces acute inflammation and increases the release of pro-inflammatory cytokines. However, current studies on mechanism of RT-induced inflammation are limited. In this study, to evaluate the relationship between miRNAs and RT-induced inflammation, RNA sequencing (RNA-Seq) was used to analyze the expression of miRNAs and mRNAs in RT-treated RAW264.7 macrophage cells. A total of 14 significantly differently expressed (DE) miRNAs and 323 miRNA-mRNA interaction pairs were predicted by bioinformatics analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that majority of those interaction pairs were involved in PI3K/Akt pathway. In addition, overexpression of miR-221-5p promoted the inflammatory response by inhibiting the mRNA expression of COL4a5. This work contributes to our understanding of RT-induced inflammation and demonstrates the potential role of miRNAs in innate immunity, which may be regarded as potential targets in developing therapies for RT poisoning. Highlights: MiR-221-5p motivated the inflammation responses by regulating COL4a5. Target genes significantly enriched in PI3K/Akt, MAPK, Ras signaling pathways. MiR-221-5p may be regarded as potential targets in developing therapies for ricin toxin poisoning.