{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The long non‐coding RNA A2M‑AS1 has emerged as a multifunctional regulator in diverse human diseases. In breast cancer, for instance, A2M‑AS1 is notably upregulated and its increased expression correlates with aggressive tumor phenotypes (ER‑negative, HER2‑positive, basal‑like) as well as poor recurrence‑free and metastasis‑free survival. Mechanistic studies in breast cancer further suggest that A2M‑AS1 promotes cell proliferation, invasion, and migration by modulating downstream factors in the cell adhesion molecule pathway and by acting as a molecular sponge for microRNAs (e.g. miR‑146b) to upregulate targets such as MUC19 and consequently alter Hippo signaling ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "]."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of myocardial ischemia/reperfusion injury, A2M‑AS1 appears to play a protective role. Its expression is downregulated in hypoxia/reoxygenation‑induced cardiomyocytes, and forced overexpression rescues cell viability while reducing apoptosis and oxidative stress. This cardioprotective function has been attributed to the regulation of the A2M‑AS1/IL1R2 axis as well as to exosomal delivery of A2M‑AS1 that modulates miR‑556‑5p/XIAP signaling ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "]."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In several cancers, including gastric cancer, non‑small cell lung cancer, and lung adenocarcinoma, A2M‑AS1 has been identified as a hub long non‑coding RNA within competing endogenous RNA networks and co‑expression analyses, associating its dysregulated expression with tumor progression and overall survival; similarly, aberrant DNA methylation at the A2M‑AS1 locus has been linked to increased breast cancer risk following exposure to environmental toxicants ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "].\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additional studies have implicated A2M‑AS1 in noncancerous conditions as well. In chronic obstructive pulmonary disease, interaction networks involving A2M‑AS1 (together with miR‑122‑5p and other lncRNAs) may contribute to the disease’s pathogenesis irrespective of smoking status, and in myocardial infarction, A2M‑AS1 has been identified as a potential biomarker for predicting recurrence ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "]. Moreover, in pancreatic ductal adenocarcinoma, A2M‑AS1 is emerging as a prognostic biomarker that might offer new avenues for early diagnosis and targeted therapy ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "]. \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight that A2M‑AS1 plays critical, context‑dependent roles—functioning as either an oncogenic driver or a protective factor—thereby representing a promising diagnostic, prognostic, and therapeutic target across multiple disease settings.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kai Fang, Hu Caixia, Zhang Xiufen, et al. 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