{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐589 (including its 3p and 5p isoforms) exerts context‐dependent regulatory effects on cell proliferation, migration, invasion, and epithelial–mesenchymal transition in cancers. In glioblastoma, for example, nearly complete editing of miR‐589‑3p in the normal brain is lost in tumor tissue; the edited version suppresses glioblastoma cell proliferation, migration, and invasion by retargeting from a tumor‐suppressor (PCDH9) to a pro‐invasion factor (ADAM12), whereas the unedited form exerts oncogenic effects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In hepatocellular carcinoma, two separate studies report that miR‐589‑5p is upregulated and functions to promote cancer stem cell characteristics, chemoresistance, and cell proliferation by targeting negative regulators of STAT3 signaling and MIG‑6."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Conversely, in prostate and endometrial cancers, miR‑589‑5p is downregulated, and its overexpression inhibits cell viability, migration, and invasion by targeting genes such as CCL5 and TRIP6."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, in breast cancer, a long noncoding RNA (TINCR) acts as a sponge to sequester miR‑589‑3p, thereby upregulating IGF1R/AKT signaling to promote tumor progression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", while in triple negative breast cancer a miR‑589‑5p/HDAC3 axis has been implicated in modulating oncogenic cell development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional evidence supports roles for miR‑589‑5p in regulating histone deacetylase–dependent and cytoskeletal pathways. In non‐small cell lung cancer, miR‑589‑5p reduces HDAC5 expression through direct targeting of its 3′‑UTR, thereby impacting cell cycle control and epithelial–mesenchymal transition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In gastric cancer, sponging of miR‑589‑5p by circCASP9 leads to dysregulation of KANK1 and promotes malignant cell behaviors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In the context of fibrotic and degenerative diseases, miR‑589 modulates TGF‑β1–induced EMT in peritoneal mesothelial cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and bioinformatics profiling in intervertebral disc degeneration has identified miR‑589 as a pivotal regulator interacting with pathways involving SMAD4 and cell cycle genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOutside of oncogenesis, miR‑589‑5p is involved in modulating oxidative stress and cellular injury. In neuronal cells exposed to hydrogen peroxide, decreased levels of the circular RNA circPRKCI result in accumulated miR‑589‑5p, which in turn reduces expression of the transcription factor E2F7 and contributes to cytotoxicity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Similarly, in brain microvascular endothelial cells, overexpression of circ_0003423 alleviates ox‑LDL–induced injury by sponging miR‑589‑5p, thereby restoring TET2 levels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " In diabetic retinopathy, upregulation of circ‑UBAP2 under high‐glucose conditions sequesters miR‑589‑5p, which leads to increased expression of EGR1 and enhanced oxidative stress and vascular dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Valeriana Cesarini, Domenico A Silvestris, Valentina Tassinari, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Maintenance of stemness by miR-589-5p in hepatocellular carcinoma cells promotes chemoresistance via STAT3 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2017.11.031"}], "href": "https://doi.org/10.1016/j.canlet.2017.11.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29196128"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29196128"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "M Xu, Y Wang, H T He, et al. 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