{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LBX2‐AS1 is a long non‐coding RNA that is frequently dysregulated in a wide range of human diseases, particularly in various cancers, where its upregulation is closely associated with aggressive clinicopathological features and poor patient outcomes. In esophageal squamous cell carcinoma, for instance, LBX2‐AS1 is markedly overexpressed and promotes cell migration and epithelial–mesenchymal transition by enhancing the stability of key transcription factors such as ZEB1 and ZEB2 through interactions with RNA‐binding proteins like HNRNPC."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In gastric cancer, LBX2‐AS1 is activated by transcription factors (for example, NFIC and ELK1) and functions as a competing endogenous RNA (ceRNA), sequestering microRNAs including miR‐219a‐2‑3p, miR‐491‑5p, and miR‐4766‑5p to upregulate oncogenic targets such as FUS, ZNF703, and CXCL5, thereby enhancing proliferation, migration, and invasion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": " In non‐small cell lung cancer, LBX2‐AS1 similarly promotes proliferation, migration, and invasion—in part by activating the Notch signaling pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In colorectal cancer, multiple studies have demonstrated that LBX2‐AS1 exerts oncogenic effects by stabilizing mRNAs (for example, via its interaction with PTBP1 to enhance KAT2A stability) as well as by acting as a ceRNA that sponges microRNAs (such as miR‐422a and miR‐491‐5p), resulting in the upregulation of targets like AKT1 and S100A11."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": " In glioma, LBX2‐AS1 facilitates tumor cell proliferation, migration, and invasion—mediated via the Akt/GSK3β pathway—and its expression is incorporated into prognostic risk models for diffuse gliomas."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In ovarian cancer, LBX2‐AS1 is transcriptionally activated by ELK1 and contributes to tumor progression by sponging microRNAs such as miR‐4784 and miR‐455‑5p/miR‐491‑5p to regulate targets like KDM5C and E2F2, thereby promoting cell proliferation, migration, and stemness; it has also been linked to modulation of drug response."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n LBX2‐AS1 is further implicated in thyroid cancers; analyses in papillary thyroid carcinoma have revealed that it is integrated within ceRNA networks that include other deregulated non‐coding RNAs, supporting its potential as a diagnostic biomarker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond oncological disorders, aberrant LBX2‐AS1 expression has been observed in non‐malignant conditions. For example, in periodontitis, ceRNA network analyses suggest its involvement in disease pathogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "; in abdominal aortic aneurysm, a positive feedback loop between LBX2‐AS1 and LBX2 contributes to pro‐apoptotic and anti‐proliferative effects in vascular smooth muscle cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "; and in cerebral cavernous malformations, differential LBX2‐AS1 expression correlates with altered vascular signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, LBX2‐AS1 is incorporated into prognostic lncRNA signatures for glioblastoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": ", underscoring its promise as a biomarker, while its modulation—through mechanisms such as METTL3‐dependent m6A methylation—also influences chemoresistance in colorectal cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Collectively, these findings indicate that LBX2‐AS1 plays multifaceted roles in regulating proliferation, apoptosis, migration, invasion, and therapy responsiveness, making it a promising diagnostic and prognostic marker as well as a potential therapeutic target across diverse disease contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "17"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "18"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "21"}, {"type": "fg_f", "ref": "13"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "20"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "14"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "15"}, {"type": "fg_f", "ref": "19"}, {"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yanshan Zhang, Weizuo Chen, Tingting Pan, et al. 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