{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMembrane-anchored serine proteases, such as TMPRSS13, play essential roles in mammalian development and tissue homeostasis. In murine models, disruption of Tmprss13 compromised skin barrier function, underscoring its developmental importance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, heightened expression of TMPRSS13 in breast cancer has been linked to increased tumor burden, enhanced proliferation, and invasive capacity, suggesting an oncogenic role that may be therapeutically targeted."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to these protein‐based regulatory mechanisms, recent investigations have highlighted the role of microRNAs in disease processes. Notably, miR‑3146 has been shown to regulate the formation of neutrophil extracellular traps (NETs), a process that contributes directly to the inflammatory milieu characteristic of gout. This regulatory function implicates miR‑3146 as a key mediator in the pathogenesis of gout, where NET formation plays a central role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTogether, these findings illustrate a complex regulatory network in which both proteolytic enzymes and microRNAs orchestrate critical biological functions. While TMPRSS13 influences tissue integrity and tumor progression, miR‑3146 specifically modulates innate immune responses through NET formation during gout. Elucidating the precise mechanisms of miR‑3146 may offer promising avenues for therapeutic intervention in inflammatory arthritis.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Daniel H Madsen, Roman Szabo, Alfredo A Molinolo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMPRSS13 deficiency impairs stratum corneum formation and epidermal barrier acquisition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20140337"}], "href": "https://doi.org/10.1042/BJ20140337"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24832573"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24832573"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Andrew S Murray, Thomas E Hyland, Kimberley E Sala-Hamrick, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The cell-surface anchored serine protease TMPRSS13 promotes breast cancer progression and resistance to chemotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-020-01436-3"}], "href": "https://doi.org/10.1038/s41388-020-01436-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32868877"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32868877"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lizhen Shan, Di Yang, Fabo Feng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-3146 induces neutrophil extracellular traps to aggravate gout flare."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Lab Anal (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcla.24032"}], "href": "https://doi.org/10.1002/jcla.24032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34606644"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34606644"}]}]}]}