{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMiR‐4521 has emerged as a significant regulator in several malignancies. In one study on gastric carcinoma, an array of candidate microRNAs was identified with potential relevance to metastasis, prompting further exploration of their modulatory roles in tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In esophageal cancer, miR‐4521 was incorporated into a prognostic risk model, with its altered expression correlating with tumor aggressiveness, immune infiltration, and other microenvironment features."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, functional experiments in medulloblastoma demonstrated that loss of miR‐4521 leads to upregulation of the oncogenic transcription factor FOXM1 and its downstream effectors, thereby promoting cell proliferation, invasion, and aberrant cell cycle progression—findings that underscore its tumor‐suppressive role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Broader studies in hepatocellular carcinoma further reinforce the significance of microRNAs in oncogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", while investigations in breast cancer have revealed that sequences of miR‐4521 are embedded within tRNA‐derived fragments (tRFs), suggesting a dual biomarker potential that warrants additional study."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n \nIn the context of neurological disorders, notably in patients with refractory epilepsy associated with focal cortical dysplasia, hsa‐miR‐4521 was found to be markedly up‐regulated in both brain tissue and serum. This significant elevation positions miR‐4521 as a promising diagnostic biomarker for early identification of such epileptogenic pathologies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n \nIn studies addressing cardiovascular complications related to type 2 diabetes, dysregulated MIR4521 expression has been implicated in vascular endothelial dysfunction. Mechanistic insights revealed that the circular RNA circHMGCS1 acts as a sponge for MIR4521, leading to overexpression of arginase 1, reduced nitric oxide secretion, enhanced production of reactive oxygen species, and increased expression of adhesion molecules—factors that collectively impair vasodilation and exacerbate endothelial injury. These findings highlight the potential therapeutic value of modulating MIR4521 to attenuate diabetes‐associated vascular damage."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shan Xing, Zhi Tian, Wenying Zheng, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "MiR-4521 plays a tumor repressive role in growth and metastasis of hepatocarcinoma cells by suppressing phosphorylation of FAK/AKT pathway via targeting FAM129A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Adv Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jare.2021.05.003"}], "href": "https://doi.org/10.1016/j.jare.2021.05.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35127170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35127170"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shaharbhanu A Hussain, Kunhi Valappil Deepak, Dechamma Pandyanda Nanjappa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comparative expression analysis of tRF-3001a and tRF-1003 with corresponding miRNAs (miR-1260a and miR-4521) and their network analysis with breast cancer biomarkers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11033-021-06732-z"}], "href": "https://doi.org/10.1007/s11033-021-06732-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34661810"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34661810"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xiaofeng Wang, Yuqiang Sun, Zeshi Tan, et al. 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