{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNR2F1‐AS1 is a long non‐coding RNA that has emerged as a key regulator of cancer cell behavior by modulating genes involved in chemoresistance and proliferation. In hepatocellular carcinoma, NR2F1‐AS1 is up‐regulated in oxaliplatin‐resistant tumors, where it sponges miR‑363 to promote ABCC1 expression and thereby enhances drug resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similar mechanisms have been observed in endometrial cancer, in which NR2F1‐AS1 facilitates cell viability, migration and invasion by downregulating miR‑363 to increase SOX4 expression and activate the PI3K/AKT/GSK‑3β pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In papillary thyroid carcinoma, NR2F1‐AS1 promotes proliferation and invasion by binding to miR‑423‑5p, which leads to the up‐regulation of SOX12."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in chemoresistance and proliferation, NR2F1‐AS1 has been implicated in the regulation of metastasis, tumor dormancy and angiogenesis. In breast cancer, NR2F1‐AS1 enhances angiogenesis by sponging miR‑338‑3p to up‐regulate IGF‑1 expression and subsequently activate the IGF‑1R/ERK pathway, while another study demonstrated that its overexpression confers a quiescence‐like state that contributes to late recurrence in estrogen receptor–positive tumors"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, in a model of metastatic dormancy, NR2F1‐AS1 was found to bind NR2F1 mRNA and recruit PTBP1 to enhance IRES‐mediated NR2F1 translation, which in turn suppresses ΔNp63 transcription and triggers epithelial–mesenchymal transition (EMT)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In gastric cancer, this lncRNA promotes EMT and tumor progression via a ceRNA network involving miR‑29a‑3p and VAMP7"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", while its aberrant expression has also been associated with invasive characteristics in esophageal squamous cell carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and melanoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Furthermore, in breast cancer metastasis, NR2F1‐AS1 facilitates cell migration and invasion through sequestration of miR‑25‑3p to stabilize the EMT transcription factor ZEB2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond these cancer contexts, NR2F1‐AS1 exhibits diverse roles that are context‐dependent. In pancreatic cancer, hypoxia‐induced NR2F1‐AS1 promotes the expression of its neighboring gene NR2F1, thereby activating the AKT/mTOR pathway and up‐regulating HIF‑1α to stimulate proliferation, migration and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In colorectal cancer, however, NR2F1‐AS1 is downregulated and its overexpression suppresses cell proliferation via the miR‑371a‑3p/TOB1 axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Its oncogenic potential is further underscored in osteosarcoma, where NR2F1‐AS1 sponges miR‑485‑5p and miR‑1218‑15p to modulate BIRC5 expression, thereby promoting tumor aggressiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Additionally, in intervertebral disc degeneration, NR2F1‐AS1 enhances extracellular matrix degradation and apoptosis via the miR‑145‑5p/FOXO1 pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Comprehensive reviews and meta-analyses have further consolidated the view that NR2F1‐AS1 influences tumorigenesis through sponging a variety of microRNAs and modulating key signaling cascades, highlighting its potential as both a prognostic biomarker and a therapeutic target across diverse malignancies"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " Notably, its role in neuroblastoma has also been examined, although the precise molecular mechanisms in this context remain to be fully elucidated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hai Huang, Jie Chen, Cheng-Ming Ding, et al. 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