{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Long non‐coding RNA HOXA‐AS3 functions as an important oncogenic and regulatory transcript in multiple human diseases by modulating diverse cellular processes including proliferation, migration, invasion, apoptosis, and chemoresistance. In glioblastoma, HOXA‐AS3 is markedly upregulated and promotes cell growth and epithelial–mesenchymal transition by acting as a competing endogenous RNA that sponges miR‐455–5p, thereby upregulating its downstream target USP3."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In lung adenocarcinoma, HOXA‐AS3 stabilizes HOXA6 mRNA through formation of an RNA duplex and its subcellular distribution is controlled via binding to NF110; its expression is further enhanced by histone acetylation, supporting tumor cell progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In pulmonary arterial hypertension, HOXA‐AS3 promotes vascular smooth muscle cell proliferation and migration by sponging miR‐675–3p, which increases PDE5A expression and contributes to aberrant cell survival under hypoxic conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Furthermore, conserved from early vertebrate evolution, HOXA‐AS3 participates in the coordinated regulation of overlapping HOX gene expression during development and cell differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, HOXA‐AS3 exerts oncogenic roles in colorectal, pancreatic, bladder, and oral squamous cell carcinomas, where it functions as a molecular sponge for distinct microRNAs (for example, miR‐4319 in colorectal cancer, miR‐29c in pancreatic cancer, and miR‐455–5p in bladder cancer) to modulate key targets such as SPNS2, CDK6, and Notch1, thereby activating downstream signaling pathways including AKT and promoting chemoresistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, these findings indicate that HOXA‐AS3 contributes to tumorigenesis and disease progression by acting as a ceRNA that fine‐tunes gene expression and epigenetic states. Its dysregulation across multiple cancers and vascular disorders correlates with aggressive clinical behavior and poor prognosis, rendering HOXA‐AS3 a promising candidate both as a prognostic biomarker and as a therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wanghao Chen, Qiaoyu Li, Guilong Zhang, et al. 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