{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Accumulating evidence indicates that the long noncoding RNA MACC1‐AS1 functions as a potent oncogenic regulator in a diverse array of cancers—including gastric, hepatic, pancreatic, breast, nasopharyngeal, non‐small cell lung, esophageal, and cervical carcinomas—where its upregulation correlates with poor prognosis. Mechanistically, MACC1‐AS1 primarily acts as a competitive endogenous RNA (ceRNA) by sponging tumor‐suppressive microRNAs (e.g."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ", thereby stabilizing and upregulating oncogenic targets such as MACC1, PAX8, and CDK6. In gastric cancer, MACC1‐AS1 is induced by mesenchymal stem cell–secreted TGF‐β and enhances fatty acid oxidation‐dependent stemness and chemoresistance, while also promoting metabolic plasticity via stabilization of MACC1 mRNA."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In hepatocellular carcinoma, MACC1‐AS1 antagonizes miR‐145 activity to promote stemness, proliferation, and migration"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", and similar ceRNA mechanisms underlie its role in nasopharyngeal and cervical cancers via modulation of Smad2 and CDK6, respectively."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In pancreatic, breast, and non‐small cell lung cancers, MACC1‐AS1 facilitates tumor growth and metastasis by upregulating oncogenic signaling pathways—including AKT/mTOR, NOTCH1, and the Hippo pathway through its interaction with factors such as UPF1."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": " In esophageal squamous cell carcinoma, NSD2‐induced MACC1‐AS1 expression contributes to cisplatin resistance"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", whereas in the context of hypoxia‐induced injury in brain microvascular endothelial cells, MACC1‐AS1 appears to play a protective role by modulating the miR‐6867‐5p/TWIST1 axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, MACC1‐AS1 emerges as a multifaceted regulator of tumor progression, metabolic reprogramming, stemness, and therapeutic resistance, highlighting its potential as both a biomarker and a promising therapeutic target in various malignancies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "13"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "11"}, {"type": "fg_f", "ref": "14"}, {"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wanming He, Bishan Liang, Chunlin Wang, et al. 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