{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GATA6‐AS1 is an evolutionarily conserved long noncoding RNA transcribed in a divergent orientation from the cardiac transcription factor GATA6 that plays multifaceted roles in both normal development and tumorigenesis. In developmental contexts, GATA6‐AS1 is robustly expressed during human definitive endoderm differentiation and cardiomyocyte specification, where it acts to upregulate its neighboring gene GATA6 by interacting with transcriptional regulators (such as SMAD2/3) to drive lineage‐specific gene expression (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In contrast, a number of studies in distinct cancer types including lung adenocarcinoma, non‐small cell lung cancer, lung squamous cell carcinoma, gastric cancer and ovarian cancer have demonstrated that GATA6‐AS1 is frequently downregulated and functions as a tumor suppressor. In these malignancies, restoration of GATA6‐AS1 expression leads to inhibition of cell proliferation, migration, invasion and epithelial–mesenchymal transition, with molecular mechanisms that include acting as a competitive endogenous RNA to sequester oncogenic microRNAs (for instance, miR‐4530 in lung adenocarcinoma, miR‐19a‐5p in ovarian cancer and miR‐324‐5p in lung cancer) as well as modulating critical signaling pathways such as the Wnt/β‐catenin and MAPK cascades."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "9"}]}, {"type": "t", "text": " Moreover, in pancreatic ductal adenocarcinoma and lung squamous cell carcinoma, its expression levels correlate with patient survival, underscoring its potential as a prognostic biomarker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Additional evidence points to roles in chromatin organization and epigenetic regulation, suggesting that GATA6‐AS1 may also influence transcriptional landscapes by recruiting chromatin modifiers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Finally, integrative functional characterization in cardiovascular disease models further supports its significant role in heart biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jie Yang, Pei Lu, Mao Li, et al. 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