{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nFOXP1 is a multifaceted transcription factor whose function is highly context‐dependent. In embryonic stem cells, an evolutionarily conserved alternative splicing event modulates its DNA‐binding preference so that an ESC‐specific FOXP1 isoform stimulates the expression of key pluripotency genes (OCT4, NANOG, NR5A2, and GDF3), thereby maintaining self‐renewal (as reported in."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, emerging evidence indicates that noncoding circular RNAs derived from the FOXP1 locus (circFOXP1) control mesenchymal stem cell identity and differentiation through regulation of non‐canonical Wnt and EGFR pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the lymphoid compartment, FOXP1 plays complex roles in B‐cell development and lymphomagenesis. Chromosomal translocations juxtaposing FOXP1 to the immunoglobulin heavy chain locus have been identified in MALT lymphomas"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and immunohistochemical studies have revealed aberrantly high FOXP1 protein levels in subsets of B‐cell lymphomas, often attributable to alternative splicing events that generate N‐terminally truncated isoforms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In these diseases, FOXP1 expression is associated with transcriptional repression of proapoptotic genes, modulation of major histocompatibility complex class II (MHC II) expression via interaction with NF‐κB pathways, and is regulated by microRNAs such as miR‐150 and miR‐34a."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": " Moreover, studies in diffuse large B‐cell lymphoma (DLBCL) have underscored the prognostic significance of FOXP1 abnormalities, with high expression correlating with poor clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFOXP1 also plays a critical role in neurodevelopment. Heterozygous mutations and deletions in FOXP1 are causative for neurodevelopmental disorders characterized by intellectual disability, language impairments, and autistic features."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "20"}]}, {"type": "t", "text": " In a brain‐specific Foxp1 knockout mouse model, loss of FOXP1 disrupts the development and function of the striatum and hippocampus, correlating with defects in neuronal morphogenesis and altered excitability in CA1 neurons."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond the nervous and immune systems, FOXP1 functions in a variety of solid tumors. In breast cancer, FOXP1 has been implicated in the maintenance of cancer stem cell properties through a PRMT5‐dependent mechanism that promotes the expression of stemness-associated genes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": ", while in breast tumors FOXP1 gene alterations at 3p14 suggest a tumor suppressor role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": " In ovarian cancer, FOXP1 contributes to autophagy and cisplatin resistance via a miR-29c-3p/ATG14 axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": ", and in prostate cancer, FOXP1 is androgen-regulated and functions to repress AR-driven transcription."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": " In lung adenocarcinoma, a LINC01614/miR-217/FOXP1 pathway has been shown to promote tumorigenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": ", and in brown/beige adipocytes, FOXP1 represses β3-adrenergic receptor transcription to modulate thermogenesis and energy balance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional roles for FOXP1 include regulation of monocyte-to-macrophage differentiation via transcriptional suppression of the c-fms gene"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": ", and participation in inflammation-associated carcinogenesis in nasopharyngeal and gastric cancers through targeting by viral microRNAs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": " FOXP1 is also implicated in cardiac gene regulation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "30"}]}, {"type": "t", "text": ", and its transcriptional activity relies on conserved domains that promote homo- and heterodimerization—for example, with FOXP2, a partner important for vocal learning and language development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "31"}]}, {"type": "t", "text": " Finally, dysregulation of FOXP1 through copy number variations or chromosomal translocations is frequently observed in lymphomas"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "33", "end_ref": "36"}, {"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", underscoring its utility as a prognostic biomarker in diffuse large B-cell lymphoma and related disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}, {"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mathieu Gabut, Payman Samavarchi-Tehrani, Xinchen Wang, et al. 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