{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMiR‐595 has emerged as a multifunctional microRNA implicated in a wide array of human diseases. Circulating microRNAs have been shown to serve as promising biomarkers in inflammatory conditions such as Crohn’s disease and ulcerative colitis, suggesting a potential diagnostic role for members of this family. Moreover, miR‐595 has been linked to the modulation of autophagy through its targeting of ULK1 in neurodegenerative models, thereby underscoring its relevance in the maintenance of cellular homeostasis and its promise as a therapeutic target."}, {"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 context of cancer, miR‐595 exhibits context‐dependent, and at times contradictory, functions. In glioblastoma, for example, miR‐595 is significantly upregulated and acts as a tumor promoter by enhancing cell proliferation through suppression of the tumor suppressor gene SOX7. By contrast, in ovarian cancer and hepatocellular carcinoma the microRNA is frequently downregulated; in these settings, restoration of miR‐595 expression suppresses tumor cell proliferation, colony formation, invasion, and improves chemosensitivity—effects that are mediated via direct targeting of genes such as ABCB1 and inhibition of the NF‑κB signaling pathway. In addition, studies in myelodysplastic syndrome with monosomy 7 or isolated 7q deletion have revealed that loss of miR‐595 results in upregulation of targets like RPL27A, which in turn perturbs p53 dynamics and ribosomal integrity, ultimately affecting cell growth. The clinical relevance of miR‐595 is further supported by correlations between its expression level and clinicopathologic features in epithelial ovarian cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in tumorigenesis, miR‐595 also modulates therapeutic responses. In paediatric acute lymphoblastic leukaemia, a polymorphism in the 3′‐untranslated region of the gene SLC19A1, which encodes the reduced folate carrier RFC1, affects miR‐595 binding. This interaction leads to downregulation of RFC1 protein expression, diminished methotrexate uptake, and reduced drug‐induced cytotoxicity, highlighting miR‐595 as an important phenotypic regulator of chemotherapeutic sensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, integrated analysis of competing endogenous RNA networks has identified miR‐595 as a key component of a circulatory RNA biomarker panel for colorectal cancer. When evaluated alongside select long non‐coding RNAs and mRNAs, miR‐595 expression reliably distinguishes colorectal cancer patients from individuals with benign colorectal neoplasms and healthy controls, suggesting its utility not only for diagnosis but also for prognostication in clinical oncology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Geoffrey W Krissansen, Yi Yang, Fiona M McQueen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of miR-595 and miR-1246 in the sera of patients with active forms of inflammatory bowel disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Inflamm Bowel Dis (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MIB.0000000000000285"}], "href": "https://doi.org/10.1097/MIB.0000000000000285"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25628040"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25628040"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yi Chen, Shuya Wang, Lan Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of ULK1 as a novel biomarker involved in miR-4487 and miR-595 regulation in neuroblastoma SH-SY5Y cell autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep11035"}], "href": "https://doi.org/10.1038/srep11035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26183158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26183158"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yu Hao, Shubao Zhang, Shaojun Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-595 targeting regulation of SOX7 expression promoted cell proliferation of human glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2016.03.008"}], "href": "https://doi.org/10.1016/j.biopha.2016.03.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27133048"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27133048"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Heba A Alkhatabi, Donal P McLornan, Austin G Kulasekararaj, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RPL27A is a target of miR-595 and may contribute to the myelodysplastic phenotype through ribosomal dysgenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.10293"}], "href": "https://doi.org/10.18632/oncotarget.10293"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27374104"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27374104"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Songyu Tian, Mingyue Zhang, Xiuwei Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-595 sensitizes ovarian cancer cells to cisplatin by targeting ABCB1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.13526"}], "href": "https://doi.org/10.18632/oncotarget.13526"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27893429"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27893429"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Q-H Zhou, Y-M Zhao, L-L Jia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mir-595 is a significant indicator of poor patient prognosis in epithelial ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2017)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29077170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29077170"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hongying Wang, Fang Jiang, Weiying Liu, et al. 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