{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent evidence indicates that hsa‐miR-4639-5p plays a crucial role in post-transcriptional gene regulation in diverse biological systems. In one study on craniofacial development, a polymorphism in the 3′-untranslated region (3′-UTR) of BMP2 was found to alter the binding affinity of miR-4639-5p. Functional assays demonstrated that enhanced miR-4639-5p binding leads to a reduction in BMP2 mRNA expression, an effect associated with an increased risk of non-syndromic tooth agenesis, particularly affecting mandibular incisor formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn a parallel line of investigation, hsa-miR-4639-5p has been identified as a key regulator in neuronal antioxidative defenses. Elevated levels of this miRNA suppress the expression of DJ-1, a protein critical for cellular protection against oxidative stress. This downregulation not only exacerbates oxidative damage leading to neuronal death but also contributes to the pathology of Parkinson’s disease. Further mechanistic studies revealed that miR-4639-5p expression is governed by a specific promoter element influenced by histone deacetylase activity, with certain promoter polymorphisms correlating with increased miRNA levels and heightened PD risk."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings highlight the multifaceted impact of hsa-miR-4639-5p in human disease. Whether modulating BMP2 expression to influence craniofacial development or regulating DJ-1 to affect neuronal survival, miR-4639-5p emerges as a pivotal molecular player. Its dual role not only provides insight into the etiology of conditions as disparate as tooth agenesis and Parkinson’s disease, but also positions it as a promising diagnostic marker and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yun Lu, Yajing Qian, Jinglu Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic Variants of BMP2 and Their Association with the Risk of Non-Syndromic Tooth Agenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0158273"}], "href": "https://doi.org/10.1371/journal.pone.0158273"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27362534"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27362534"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lu He, Yimeng Chen, Suzhen Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of Hsa-miR-4639-5p expression and its potential role in the pathogenesis of Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging Cell (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/acel.13840"}], "href": "https://doi.org/10.1111/acel.13840"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37101349"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37101349"}]}]}]}