{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HOTAIRM1 is a long non‐coding RNA transcribed from the HOXA cluster that plays diverse, context‐dependent roles in both normal differentiation and tumorigenesis. In glioblastoma and pancreatic ductal adenocarcinoma, HOTAIRM1 is frequently overexpressed, where it contributes to tumor progression by promoting cell proliferation, migration, invasion, and by altering cell cycle dynamics through epigenetic regulation of HOXA genes and modulation of histone modifications."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In the immune context, HOTAIRM1 is implicated in myeloid cell development; its expression enhances HOXA1 levels in myeloid‐derived suppressor cells, thereby downregulating immunosuppressive factors and modulating anti-tumor immunity, as observed in lung cancer models and in chronic viral infections."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In differentiation processes, HOTAIRM1 fosters osteogenesis in mesenchymal stem cells and dental follicle stem cells by activating key osteogenic transcription factors—such as RUNX2 and HOXA2—via interactions with histone modifiers and DNA methylation regulators."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the kidney, a predominant cytoplasmic isoform of HOTAIRM1 (HM1-3) is necessary for renal lineage differentiation and appears to suppress hypoxia-inducible angiogenic pathways in clear cell renal cell carcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, in thyroid cancer, HOTAIRM1 is upregulated and contributes to tumor progression by regulating microRNA-mediated signaling pathways, such as the miR-148a/Wnt10b axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", whereas in acute promyelocytic leukemia, reduced HOTAIRM1 levels—linked to increased Skp2 activity—impair differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Collectively, these studies underscore the multifaceted regulatory functions of HOTAIRM1 in modulating gene expression via epigenetic mechanisms and microRNA sponging, which in turn affect cell differentiation, immune responses, and tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Qi Li, Chengya Dong, Jiayue Cui, et al. 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