{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR‐146b is a multifunctional microRNA that plays a central role in fine‐tuning inflammatory and stress‐related signaling pathways as well as in regulating cancer cell behavior. In breast cancer cells, for example, forced expression of miR‐146b (often in tandem with miR‐146a) suppresses nuclear factor–κB (NF‐κB) activity by directly targeting key adapter proteins such as interleukin‐1 receptor–associated kinase and TNF receptor–associated factor 6, resulting in reduced cytokine production and impaired migratory and invasive capacities. In parallel, in pro‐inflammatory settings such as activated endothelial cells and monocytes, miR‐146b is transcriptionally induced by signals including IL‐1 and IL‐10, establishing a negative feedback loop that dampens Toll‐like receptor (TLR)–mediated NF‐κB and MAP kinase pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, miR‐146b exhibits context‐dependent functions. In several tumor types—including glioblastoma, hepatocellular carcinoma and diffuse large B‐cell lymphoma—miR‐146b‐5p acts as a tumor suppressor by targeting pro‐oncogenic molecules such as epidermal growth factor receptor (EGFR), matrix metalloproteinase 16 (MMP16) and components of the TLR pathway, leading to reduced tumor cell proliferation, invasion and migration. Conversely, in thyroid and certain breast cancers, miR‐146b is frequently overexpressed and functions to modulate epithelial–mesenchymal transition and differentiation by targeting genes such as SMAD4, BRCA1, phosphatase and tensin homolog (PTEN) and PAX8; such regulation contributes to altered cell survival, therapy responsiveness, and even aggressive tumor behavior. Additional studies in non–small cell lung cancer and papillary thyroid carcinoma underscore its prognostic value, whereas its dysregulation can be driven by competing endogenous RNAs in cancers like renal cell carcinoma and cervical cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cancer and inflammation, miR‐146b also contributes to normal physiological processes. In hematopoietic stem and progenitor cells, miR‐146b is part of an autoregulatory circuit with the transcription factor GATA‐1 that promotes erythroid and megakaryocytic differentiation. In mature adipocytes, its expression is robustly up‐regulated by pro‐inflammatory cytokines—suggesting a role in modulating obesity‐related inflammation—while in the endothelium, miR‐146b further helps restrain excessive inflammatory responses. Collectively, these findings position miR‐146b as a critical post‐transcriptional regulator whose context‐dependent actions offer promising avenues for both biomarker development and targeted therapeutic intervention across a spectrum of disease states."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "D Bhaumik, G K Scott, S Schokrpur, et al. 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