{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐520c, particularly its mature form miR‐520c‐3p, has emerged as a critical regulator of gene expression with potent tumor‐suppressive properties. In breast cancer, for example, members of the miR‐520/373 family inhibit NF‐κB signaling by directly targeting RELA, thereby reducing the production of pro‐inflammatory cytokines such as IL‐6 and IL‐8 and suppressing metastasis. In addition, elevated levels of miR‐520c‐3p repress global protein synthesis by targeting the translation initiation factor eIF4GII, and inhibit the translation of oncogenes like MT1‐MMP that are associated with tumor invasion and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nLong non‐coding RNAs also play an important role in modulating miR‐520c‐3p function. In breast cancer and osteosarcoma, the lncRNA HOXA‐AS2 acts as a molecular sponge for miR‐520c‐3p, thereby preventing it from suppressing its downstream targets such as TGFBR2 and RELA. Moreover, in breast cancer cells miR‐520c‐3p can directly target the 3′‐UTR of IL‐8, reducing its expression and consequently reversing epithelial‐to‐mesenchymal transition (EMT). In melanoma stem cells, elevated levels of miR‐520c parallel an increase in metastasis‐associated signaling, suggesting that fine‐tuning of miR‐520c expression is critical for regulating tumor progression in different cellular contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cancer, miR‐520c‐3p is instrumental in modulating inflammatory responses in diverse disease states. In glioma, lower miR‐520c levels correlate with enhanced cell migration and invasion via derepression of TGFBRII, reinforcing its tumor‐suppressive capacity. In lung adenocarcinoma, the epigenetic downregulation of miR‐520c‐3p—mediated by promoter methylation—leads to upregulation of key targets such as AKT1 and AKT2, contributing to tumor growth. Furthermore, miR‐520c‐3p attenuates inflammatory injury by targeting NLRP3 in preeclampsia and NLRC5 in acute lung injury, which collectively underscores its role as an anti‐inflammatory mediator."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nmiR‐520c‐3p also contributes to vascular homeostasis, influencing endothelial cell function and atherosclerotic processes. In atherosclerosis models, overexpression of miR‐520c‐3p reduces plaque formation by inhibiting proliferation and migration of vascular smooth muscle cells via suppression of RELA. Consistently, in human endothelial cells, miR‐520c‐3p modulates cell proliferation, adhesion, and apoptosis by regulating AKT and NF‐κB signaling pathways. In colorectal cancer, its targeting of S100A4 further demonstrates a critical role in repressing EMT and metastatic behavior."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "14"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "I Keklikoglou, C Koerner, C Schmidt, et al. 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