{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐591 (miR-591) has emerged as a key regulator of oncogenesis and chemoresistance in various cancers. In hepatocellular carcinoma, miR-591 functions as a tumor suppressor via direct targeting of far-upstream element‐binding protein 2 (FBP2). By binding to the 3′-untranslated region of FBP2, miR-591 downregulates its expression, thereby blocking the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin signaling cascade. This inhibition leads to reduced drug resistance and decreased tumorigenicity of cancer stem cells, underscoring its therapeutic potential in overcoming chemoresistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn breast cancer, miR-591 is indirectly implicated in tumor progression through its interaction with circular RNAs. Specifically, the circular RNA hsa_circ_0069094 acts as a molecular sponge for miR-591. By sequestering miR-591, circ_0069094 prevents the microRNA from repressing hexokinase 2 (HK2), a key enzyme that promotes glycolysis and supports the malignant phenotype. This interaction highlights a novel ceRNA regulatory mechanism by which downregulation of miR-591 contributes to enhanced tumor cell proliferation and metabolic reprogramming."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSimilarly, in glioma, miR-591 is part of a regulatory axis involving circABCC1. Here, circABCC1 is overexpressed and functions as an oncogene by sponging miR-591, thereby relieving miR-591-mediated repression of its target, high-mobility group A2 (HMGA2). The resulting upregulation of HMGA2 promotes glioma cell proliferation, migration, and overall tumor progression. Thus, the circABCC1/miR-591/HMGA2 signaling cascade represents an important pathway in glioma oncogenesis and provides a potential target for therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Huili Wang, Yanhua Tang, Dong Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-591 Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Lowering Drug Resistance through Inhibition of Far-Upstream Element-Binding Protein 2-Mediated Phosphoinositide 3-Kinase/Akt/Mammalian Target of Rapamycin Axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacology (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000501162"}], "href": "https://doi.org/10.1159/000501162"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31280269"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31280269"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zeyu Xing, Xin Wang, Jiaqi Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hsa_circ_0069094 accelerates cell malignancy and glycolysis through regulating the miR-591/HK2 axis in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2020.109878"}], "href": "https://doi.org/10.1016/j.cellsig.2020.109878"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33309838"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33309838"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lei Wang, Ying Tan, Jun Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CircABCC1 promotes the development of glioma by sponging miR-591 and modulating high-mobility group A2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann N Y Acad Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/nyas.14717"}], "href": "https://doi.org/10.1111/nyas.14717"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35000195"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35000195"}]}]}]}