{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMiR‐493 functions in a context‐dependent manner across a spectrum of malignancies. In several cancer types including bladder, colon, hepatocellular, melanoma, and non‐small cell lung cancers, miR‐493 exerts tumor‐suppressive effects by attenuating cell proliferation, migration, invasion, and metastasis. For example, in bladder cancer miR‐493 downregulates oncogenes such as FZD4 and RhoC to inhibit cell motility, while in colon cancer it suppresses liver metastasis by targeting key mediators including IGF1R and MKK7. Similarly, in hepatocellular carcinoma and melanoma, restoration of miR‐493 reduces tumor growth by inhibiting GP73, MYCN, VAMP2, and IRS4, and its targeting of ITGB1 in non‐small cell lung cancer is associated with improved patient outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe expression and activity of miR‐493 are frequently modulated by epigenetic mechanisms and by competitive endogenous RNA networks. In hepatocellular carcinoma, miR‐493‐5p silencing via hypermethylation contributes to tumor progression, whereas in various cancers ceRNA molecules—such as lncRNAs (e.g., CCAT2 in cervical cancer and GAS6‑AS2 in breast cancer) and circular RNAs (e.g., circPRKDC in gastric cancer and LINC00324 in esophageal squamous cell carcinoma)—sequester miR‐493‐5p. This sponging relieves suppression of downstream oncogenic targets (including CREB1, FUT4, MAPK1, and IRS2), thereby promoting cell proliferation, epithelial–mesenchymal transition, and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nConversely, in select neoplasms miR‐493 displays oncogenic properties. In BRCA1/2‐mutated ovarian cancer, miR‐493‐5p is implicated in the development of platinum and PARP inhibitor resistance through alterations in DNA repair and replication stress, and in prostate cancer its overexpression promotes proliferation by targeting the tumor suppressor PHLPP2, thereby activating Akt signaling. Moreover, modulation of miR‐493 expression by transcription factors such as Snail in head and neck cancers or via epigenetic regulation in lung cancer further emphasizes its dual and context‐specific roles in tumor biology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its cell‐intrinsic effects, extracellular miR‐493 also modulates the tumor microenvironment. Elevated levels of miR‐493‐5p in cancer‐associated fibroblast–derived exosomes have been shown to promote intrahepatic cholangiocarcinoma progression through suppression of targets such as CARTPT. Clinically, higher miR‐493 expression has been associated with favorable disease‐free survival in triple‑negative breast cancer, and its dysregulation is observed in pituitary carcinomas versus adenomas, underscoring its potential utility as a prognostic biomarker across cancer types."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "20"}, {"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gail Stilling, Zhifu Sun, Shuya Zhang, et al. 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