{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies in diverse disease contexts have revealed that microRNAs from the miR-146 family modulate key signaling pathways, albeit with context-dependent outcomes. In inflammatory skin conditions such as acne, keratinocytes exposed to biofilm-derived Cutibacterium acnes exhibit an upregulation of miR-146a following toll-like receptor 2 (TLR2) activation. This miRNA directly targets and suppresses the expression of adapter molecules IRAK1 and TRAF6, thereby attenuating downstream NF‑κB and MAPK signaling cascades and ultimately reducing the secretion of proinflammatory cytokines IL‑6, IL‑8, and TNF‑α. These findings highlight a predominantly anti‑inflammatory role in the regulation of acne pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast, in the context of pancreatic cancer, the miR‑1469‑5p isoform is significantly upregulated, with elevated levels correlating with lymph node metastasis and advanced TNM stage. Functional analyses indicate that miR‑1469‑5p exerts oncogenic effects by directly binding to and downregulating the metastasis suppressor NDRG1, which in turn leads to the activation of the NF‑κB pathway and reduction of the cell adhesion molecule E‑cadherin. This molecular axis promotes cancer cell proliferation and invasion, suggesting that miR‑1469‑5p could serve as a prognostic biomarker and potential therapeutic target in pancreatic malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nConversely, in primary cutaneous melanoma, miR‑1469 is expressed at lower levels in ulcerated tumors compared to non‑ulcerated tumors. Restoration of miR‑1469 through mimic transfection resulted in a marked decrease in melanoma cell migratory and invasive capacities, an effect at least partly mediated by reduced expression of its target gene MCL1. These data imply that miR‑1469 functions as a tumor suppressor in melanoma by specifically modulating pathways that underlie cellular invasion and migration, thereby influencing disease progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rong Zeng, Haoxiang Xu, Yuzhen Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-146a Inhibits Biofilm-Derived Cutibacterium acnes-Induced Inflammatory Reactions in Human Keratinocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jid.2019.03.1161"}], "href": "https://doi.org/10.1016/j.jid.2019.03.1161"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31194941"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31194941"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jinju Liu, Chaoyu Zhu, Lingzhi Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-1469-5p promotes the invasion and proliferation of pancreatic cancer cells via direct regulating the NDRG1/NF-κB/E-cadherin axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13577-020-00399-7"}], "href": "https://doi.org/10.1007/s13577-020-00399-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32757096"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32757096"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mallory J DiVincenzo, Zoe Barricklow, Emily Schwarz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of miR-1469 expression mediates melanoma cell migration and invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0256629"}], "href": "https://doi.org/10.1371/journal.pone.0256629"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34469478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34469478"}]}]}]}