{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR-3662 exhibits context‐dependent functional roles in cancer biology. In lung cancer, particularly non‐small cell lung adenocarcinoma, miR-3662 is upregulated in patient plasma and shows promising diagnostic performance, with its elevated expression correlating with advanced disease stages and tumor subtypes. These findings suggest that miR-3662 holds potential as a liquid biopsy biomarker for early detection and precise classification."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC), miR-3662 appears to act as a tumor suppressor. In HCC, miR-3662 is frequently downregulated, and its enforced expression dampens the Warburg effect by reducing key metabolic parameters—such as lactate production, glucose consumption, ATP generation, and cellular glucose-6-phosphate levels—while enhancing oxygen consumption. Mechanistic studies indicate that miR-3662 directly targets hypoxia-inducible factors such as HIF-1α and the glycolytic enzyme hexokinase 2 (HK2), thereby impairing cell proliferation, invasion, and cell cycle progression. In PDAC, low miR-3662 expression has been implicated in the development of chemoresistance, suggesting its potential utility in overcoming drug resistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the hematopoietic compartment, genetic variation at the 6q23.3 locus is associated with increased miR-3662 expression, which in turn promotes colony formation in normal hematopoietic progenitor cells, particularly within the erythroid lineage. Notably, while miR-3662 is virtually absent in acute myeloid leukemia (AML)—where its restoration elicits potent antileukemic effects by directly targeting NF-κB-mediated transcription—its regulatory network in adult T-cell leukemia/lymphoma (ATLL) is driven by transcription factors IRF4 and c-Rel. In ATLL cells, miR-3662 contributes to cell proliferation and is correlated with antiviral drug resistance, underscoring its multifaceted roles in hematologic malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tomasz Powrózek, Paweł Krawczyk, Dariusz M Kowalski, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "MiR-3662 suppresses hepatocellular carcinoma growth through inhibition of HIF-1α-mediated Warburg effect."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-0616-8"}], "href": "https://doi.org/10.1038/s41419-018-0616-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29748591"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29748591"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "J Ye, X Xiao, Y Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-3662 suppresses cell growth, invasion and glucose metabolism by targeting HK2 in hepatocellular carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasma (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4149/neo_2020_190730N689"}], "href": "https://doi.org/10.4149/neo_2020_190730N689"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32726127"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32726127"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "An Liu, Yonggui Zhou, Tian Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiRNA-3662 reverses the gemcitabine resistance in pancreatic cancer through regulating the tumor metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Chemother Pharmacol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00280-021-04289-z"}], "href": "https://doi.org/10.1007/s00280-021-04289-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33993382"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33993382"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sophia E Maharry, Christopher J Walker, Sandya Liyanarachchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dissection of the Major Hematopoietic Quantitative Trait Locus in Chromosome 6q23.3 Identifies miR-3662 as a Player in Hematopoiesis and Acute Myeloid Leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Discov (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/2159-8290.CD-16-0023"}], "href": "https://doi.org/10.1158/2159-8290.CD-16-0023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27354268"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27354268"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kiyoshi Yasui, Mai Izumida, Takeya Nakagawa, et al. 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