{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐519c functions as a critical post‐transcriptional regulator in multiple cellular contexts by directly binding to target mRNAs and repressing their translation. In several carcinoma cell lines, overexpression of miR‐519 (as shown in studies using its precursor) efficiently downregulates the mRNA binding protein HuR, thereby curbing HuR‐mediated stabilization of proliferation‐promoting transcripts. Similarly, miR‐519c has been shown to directly target the 3′‑UTR of hypoxia‑inducible factor‑1α (HIF‑1α), leading to its reduced protein expression and subsequent suppression of tumor angiogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the realm of drug disposition and chemoresistance, miR‑519c plays an important role by targeting the multidrug transporter ABCG2. In human breast cancer and other cell models, miR‑519c binding within ABCG2’s 3′‑UTR accelerates mRNA degradation and limits protein translation, thereby affecting intracellular drug accumulation. Moreover, in human embryonic stem cells and colorectal cancer models, lower levels of miR‑519c correlate with elevated ABCG2 expression, a condition that contributes to drug resistance. These observations underscore the miRNA’s function in modulating drug sensitivity by fine‐tuning the expression of key transporters."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nContrasting functions have been revealed in tumor progression and chemoresistance across distinct cancer types. In hepatocellular carcinoma, miR‑519c‑3p is markedly overexpressed and acts as a tumor promoter by targeting BTG3, ultimately facilitating cell proliferation, migration, and metastasis. Conversely, in esophageal squamous cell carcinoma, miR‑519 has been implicated as a tumor suppressor. In melanoma, decreased levels of miR‑519c‑3p—resulting from its sequestration by the long noncoding RNA NEAT1—contribute to cisplatin resistance, highlighting the nuanced, context‐dependent roles of miR‑519c in malignant progression and therapeutic response."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kotb Abdelmohsen, Subramanya Srikantan, Yuki Kuwano, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Escape from hsa-miR-519c enables drug-resistant cells to maintain high expression of ABCG2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Ther (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1535-7163.MCT-09-0292"}], "href": "https://doi.org/10.1158/1535-7163.MCT-09-0292"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19825807"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19825807"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xin Li, Yu-Zhuo Pan, Gail M Seigel, et al. 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