{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n EPB41L4A‐AS1 is a multifunctional long non‐coding RNA whose roles vary with cellular context and disease state. In mesenchymal stem cells, EPB41L4A‐AS1 is targeted by miR‐146a, and its downregulation is associated with reduced cell proliferation via effects on the cell cycle, whereas its ectopic overexpression promotes proliferation through modulation of cell cycle‐related signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer, EPB41L4A‐AS1 appears to have context‐dependent functions. In non‐small cell lung cancer, reduced levels correlate with tumorigenesis and poorer overall survival, suggesting a potential tumor‐suppressive role"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", while in breast cancer, low EPB41L4A‐AS1 expression is associated with enhanced cell proliferation, migration, invasion, and diminished apoptosis, indicating its function as a tumor suppressor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Conversely, in colorectal cancer, EPB41L4A‐AS1 is highly expressed and appears to drive proliferation, metastasis, and epithelial‐mesenchymal transition through activation of Rho/ROCK signaling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "; additionally, its inclusion in ceRNA networks in cervical cancer further supports its regulatory impact on tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond cell proliferation, EPB41L4A‐AS1 contributes to metabolic regulation. In type 2 diabetes mellitus, for instance, EPB41L4A‐AS1 interacts with the acetyltransferase GCN5 to modify histone marks at promoters of GLUT4/2 and TXNIP, thereby reducing glucose uptake in muscle cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In placental trophoblasts related to early recurrent miscarriage, its upregulation shifts cellular metabolism away from glycolysis and towards fatty acid oxidation by altering promoter histone modifications, which may disrupt the Warburg-like effect necessary for rapid villous growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, in the context of cancer metabolic reprogramming, EPB41L4A‐AS1 functions as a repressor of the Warburg effect by interacting with nucleolar proteins such as HDAC2 and NPM1. Its depletion increases glycolysis and glutaminolysis, thereby sensitizing tumors to glutaminase inhibitors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Finally, network analyses in various hematologic malignancies also implicate EPB41L4A‐AS1 in regulatory circuits governing cell differentiation and proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, EPB41L4A‐AS1 plays diverse roles in modulating cell proliferation, cell cycle progression, metabolic reprogramming, and inflammatory responses. Its deregulated expression in various cancers and metabolic disorders highlights its potential utility as a diagnostic biomarker and therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Penglei Cui, Xiaoying Zhao, Jinlong Liu, et al. 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