{"type": "root", "children": [{"type": "t", "text": "<div>\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Long non‐coding RNA ACTA2‐AS1 has been implicated in the progression of multiple human malignancies and other pathological conditions, acting through diverse molecular mechanisms—often as a competing endogenous RNA (ceRNA). In lung adenocarcinoma, for example, ACTA2‐AS1 is downregulated, and its overexpression restrains cell proliferation, invasion, and epithelial–mesenchymal transition while promoting apoptosis by sponging miR-378a-3p and miR-4428 to upregulate SOX7."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In ovarian cancer, ACTA2‐AS1 exhibits an opposite expression pattern; it is upregulated in cisplatin-resistant cells and contributes to chemoresistance by sequestering miR-378a-3p to modulate Wnt5a signaling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", and by acting as a ceRNA for miR-532-5p to regulate CXCL2, thereby enhancing cell proliferation and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In cisplatin-resistant non-small cell lung cancer, reduced ACTA2‐AS1 levels are associated with increased cell viability and autophagy, with its overexpression promoting apoptosis through recruitment of EZH2 to suppress TSC2 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In liver cancer, a transcript variant designated ACTA2‐AS1:4 functions as a tumor suppressor; its downregulation is correlated with enhanced proliferation, cell cycle progression, migration, and invasion, underscoring its role in curbing malignant behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Similarly, in colon (and colorectal) adenocarcinoma, ACTA2‐AS1 is markedly downregulated, and its overexpression inhibits cell proliferation and colony formation while inducing apoptosis by sponging miR-4428 to regulate BCL2L11."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n ACTA2‐AS1 has also been identified as a component of prognostic ceRNA signatures in breast"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and ovarian cancers"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", emphasizing its potential as a diagnostic and prognostic biomarker. In gastric cancer, overexpression of ACTA2‐AS1 inhibits cell viability, migration, invasion, and the epithelial–mesenchymal transition by binding miR-378a-3p."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond epithelial malignancies, ACTA2‐AS1 is also involved in non-cancerous disease contexts. In vascular smooth muscle cells subjected to stent injury, downregulation of ACTA2‐AS1 has been observed"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", while in cervical cancer, its increased expression promotes progression through sponging miR-143-3p to upregulate SMAD3."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Moreover, in biliary diseases, ACTA2‐AS1 facilitates the recruitment of the p300/ELK1 complex to target gene promoters, driving histone H3K27 acetylation and the epigenetic activation of proliferative and fibrogenic genes that contribute to ductular reactions and fibrosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies reveal that the functional role of ACTA2‐AS1 is highly context dependent: it can act as a tumor suppressor in some cancers (lung, liver, colon/colorectal, and gastric cancers) by inhibiting cell proliferation, migration, and invasion and promoting apoptosis, while in other cancers (ovarian and cervical) it promotes chemoresistance and tumor progression via ceRNA mechanisms. This multifaceted nature of ACTA2‐AS1 not only underscores its potential as a prognostic biomarker but also suggests that modulating its expression or ceRNA activity may represent a novel therapeutic strategy.\n "}]}, {"type": "t", "text": "\n</div>"}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kangtai Ying, Ling Wang, Guangyan Long, et al. 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