{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZC3H12A, which encodes the protein MCPIP1 (also known as Regnase‐1), plays a central role in regulating inflammation. Rapidly induced by proinflammatory signals such as MCP‐1, IL‐1β, TNF‐α, or LPS, MCPIP1 acts as a ribonuclease to destabilize mRNAs encoding multiple cytokines (for example, IL‐6, IL‐12, IL‐1β, IL‐2) and attenuates NF‐κB and AP1 signaling. In doing so, it establishes a negative feedback loop that limits excessive inflammatory responses in diverse tissues including the heart, brain, and immune cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its cytokine mRNA–destabilizing function, MCPIP1 exerts a pivotal role in post‐transcriptional regulation by targeting noncoding RNAs. By cleaving the terminal loops of precursor microRNAs, MCPIP1 counteracts Dicer activity and thereby suppresses miRNA maturation. This abortive processing not only reshapes the cellular miRNome but also confers broad‐spectrum antiviral activities through the direct degradation of viral RNAs from pathogens such as Japanese encephalitis virus, dengue virus, and herpesviruses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "13"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMCPIP1 also influences processes of angiogenesis, tissue remodeling, and cellular differentiation. In endothelial cells and in models of inflammatory angiogenesis, MCPIP1 modulates transcription of pro‐ and antiangiogenic factors—including VEGF, HIF‐1α, SIRT1, and cadherins—to control capillary tube formation and vascular permeability. Moreover, its regulatory activity extends to cellular differentiation programs in neural, mesenchymal, and epithelial cells, thereby linking inflammatory cues with fibrosis, endothelial–mesenchymal transitions, and epithelial homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "22"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond inflammation and differentiation, MCPIP1 functions as an important tumor suppressor and regulator of cell fate in cancer and regenerative contexts. Its RNase activity contributes not only to the destabilization of pro‐tumorigenic cytokine transcripts but also to the control of oncogenic factors and signaling pathways that govern epithelial–mesenchymal transition, cell cycle progression, and stem cell self–renewal. Through modulation of activity and stability of targets such as MYCN, regulators of the Wnt/β–catenin pathway, and other transcription factors (e.g. C/EBPβ), MCPIP1 suppresses malignant growth in settings such as neuroblastoma, renal cell carcinoma, and triple–negative breast cancer; it likewise improves inflammatory responses in adoptive T cell therapies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "38"}]}, {"type": "t", "text": ""}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Limei Zhou, Asim Azfer, Jianli Niu, et al. 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