Figure 2.

Enoxacin-induced dysregulation of miRNA biogenesis and its consequences. Enoxacin enhanced the activity of the RISC loading protein TRBP, resulting in an increase in the number of mature miRNAs. It also impairs the activity of DHX9 helicase, a member of the RISC, leading to the impairment of mRNA translational repression and degradation. On the other hand, it increases the number of GW/P bodies, the sites of RNA-mediated silencing, as well as the localization of miRNA packaging into EVs. The enoxacin-dysregulated biogenesis of miRNA is involved in osteoclastogenesis, apoptosis, DNA damage response, epithelial–mesenchymal transition, cancer cell proliferation, migration and invasiveness. Abbreviations: polymerase II (Pol II); methyltransferase-like 3 (METTL3); microprocessor complex subunit DGCR8 (DGCR8); type III RNase Drosha (Drosha); GTP-binding nuclear protein Ran (Ran); endoribonuclease DICER (DICER); TAR RNA-binding protein 2 (TRBP); Toll-like receptor (TLR); RNA-induced silencing complex (RISC); GW processing body (GW/P-body); Piwi-interacting RNA (piRNA); epithelial–mesenchymal transition (EMT); matrix metalloproteinase-2 (MMP2); DNA damage response (DDR); extracellular vesicles (EVs). MiRNA biogenesis adapted from [16]. Created with BioRender.com.