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MicroRNA 146a-5p (miR-146a-5p) is a key regulatory non-coding RNA that acts as a molecular brake on the innate immune system. It is primarily induced by the activation of Toll-like receptor 4 (TLR4) by ligands such as lipopolysaccharide (LPS), creating a negative feedback loop to prevent hyper-inflammation (Taganov et al., 2006). In macrophages and dendritic cells, miR-146a-5p targets the signaling adapters IRAK1 and TRAF6, which are essential for NF-kappaB activation (Saba et al., 2014). Furthermore, miR-146a-5p can be sequestered into exosomes and transferred between cells, allowing for the paracrine modulation of inflammatory responses in the microenvironment (Alexander et al., 2015). Dysregulation of this miR-146a-5p-mediated network is implicated in chronic inflammatory conditions, sepsis, and various malignancies (Labbaye & Testa, 2012). While no miR-146a-specific drugs are currently FDA-approved, miR-146a mimics and antagomirs are being investigated in preclinical models to treat inflammatory diseases and cancer by either restoring or inhibiting this regulatory pathway (Saba et al., 2014).
MicroRNA 146a-5p functions as a post-transcriptional repressor that binds to the 3' untranslated regions (UTRs) of target mRNAs, specifically Interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6). This binding leads to mRNA degradation or translational inhibition, which suppresses the activation of the NF-kappaB signaling pathway downstream of Toll-like receptor 4 (TLR4), thereby dampening the production of pro-inflammatory cytokines (Taganov et al., 2006; Saba et al., 2014).
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