{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LINC00667 is a long non‐coding RNA that has emerged as a key regulator across a spectrum of human diseases, with its function being most extensively characterized in various cancers as well as in renal and metabolic disorders. In chronic renal conditions, for example, silencing LINC00667 in renal tubular epithelial cells promoted cell proliferation and reduced fibrosis via the miR‐19b‐3p/connective tissue growth factor (CTGF) pathway ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "] and through modulation of miR‐34c ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "]."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the cancer arena, LINC00667 is most often overexpressed and functions as an oncogenic competing endogenous RNA (ceRNA) that sponges various tumor‐suppressive microRNAs. In non‐small cell lung cancer (NSCLC), it not only promotes proliferation, migration, and angiogenesis by recruiting factors (e.g., EIF4A3) to stabilize VEGFA mRNA ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "] but also facilitates tumor growth by regulating the miR‐143-3p/RRM2 axis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "] and is recognized as one of the dysregulated lncRNAs associated with disease progression ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "]. In cholangiocarcinoma, LINC00667 is transcriptionally activated by YY1 and sponges miR‐200c-3p to upregulate pyruvate dehydrogenase kinase 1 (PDK1), thereby enhancing cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "]. Its tumor-promoting role is also evident in pediatric Wilms’ tumor where it binds miR‐200b/c/429 to relieve repression of IκB kinase β (IKK-β) and activate the NF-κB pathway ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "]. Similarly, in esophageal cancer, LINC00667 acts as a ceRNA for miR‐200b-3p to modulate SLC2A3 expression and promote metastasis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "]. In colorectal cancer, YY1-driven upregulation of LINC00667 sequesters miR‐449b-5p, which in turn leads to enhanced YY1 expression and tumor cell proliferation and migration ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "]. In nasopharyngeal carcinoma, the LINC00667/miR‐4319/FOXQ1 axis underlies its role in stimulating cell proliferation, migration, invasion, and EMT ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "], while in hepatocellular carcinoma, LINC00667 promotes tumor progression by sponging miR‐130a-3p to relieve repression on the androgen receptor (AR) ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "].\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond solid tumors, LINC00667 is also implicated in other pathophysiological contexts. In glioma, it contributes to vasculogenic mimicry through a USF1/linc00667/miR‐429/ALDH1A1 axis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "]. Moreover, prognostic models in ovarian carcinoma and thyroid cancer incorporate LINC00667 as a biomarker for recurrence and prognosis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "], and its inclusion in an immune-related lncRNA signature has also been reported in neuroblastoma ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "]."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In metabolic and inflammatory disorders, LINC00667’s expression is linked with key immuno-metabolic processes. It is associated with inflammation, oxidative stress, and apoptosis in polycystic ovary syndrome ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "], and its decreased circulating levels have been reported in periodontitis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "]. In diabetic nephropathy, m6A methylation-mediated modifications of LINC00667 are related to macrophage M1 immune responses ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "], while in gestational diabetes mellitus, it participates in a ceRNA network involving YTHDF3, MYC, and miR‐33a-5p ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "]. Finally, in a neurodegenerative context, a positive feedback loop comprising LINC00667, miR‐34c-5p, and HNF4A has been described in a Parkinson’s disease model ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "].\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies illustrate that LINC00667 predominantly functions as an oncogenic and pro-fibrotic factor through its activity as a ceRNA that sequesters multiple microRNAs – thereby modulating critical downstream targets and signaling pathways involved in cell proliferation, migration, invasion, EMT, and angiogenesis. Its multifaceted roles also extend to the regulation of immune, inflammatory, and metabolic responses, underlining its potential as both a prognostic biomarker and a therapeutic target in diverse human diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wen Chen, Zhong-Qi Zhou, Yue-Qin Ren, et al. 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