{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR-708 has emerged as a versatile regulator of cell fate and stress responses in several organ systems. In skeletal muscle satellite cells, for example, miR-708 is induced by Notch signaling and acts to maintain quiescence as well as fine‐tune the cellular migratory capacity by targeting Tensin3, thereby contributing to efficient activation upon injury. In pancreatic islets, miR-708 is markedly upregulated under low-glucose conditions or endoplasmic reticulum stress, where it represses neuronatin (Nnat), leading to diminished glucose-stimulated insulin secretion and impaired proliferation while promoting apoptosis. Moreover, altered expression of miR-708 has been correlated with key longevity pathways—including mTOR, FOXO, and MAPK—suggesting a broader role in the aging process."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther investigations indicate that miR-708 participates in controlling fibrotic and apoptotic processes in other tissues. In the liver, its downregulation in fibrotic tissues and activated hepatic stellate cells leads to increased expression of ZEB1 and subsequent activation of the Wnt/β-catenin signaling pathway—a mechanism that favors fibrogenesis. In ocular tissues, particularly in glaucoma models, reduced levels of miR-708 in retinal ganglion cells promote autophagy via upregulation of ATG3, culminating in enhanced apoptosis. Similarly, in osteoblasts exposed to oxidative stress (e.g., H2O2), miR-708 appears to mitigate apoptosis, thereby implicating its protective role in bone homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging data also link miR-708 to metabolic regulation and joint health. Exposure to endocrine-disrupting chemicals like bisphenol A in the hypothalamus elevates miR-708-5p levels via ER stress-related pathways, leading to reduced neuronatin expression and increased levels of orexigenic neuropeptides such as Npy, a change that may contribute to altered feeding behavior and obesity. Additionally, preliminary studies in the temporomandibular joint suggest that miR-708 might be involved in transducing biomechanical signals that trigger cellular senescence in joint cartilage, thereby offering potential as a therapeutic target in degenerative conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Benjamin P Lee, Ivana Burić, Anupriya George-Pandeth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNAs miR-203-3p, miR-664-3p and miR-708-5p are associated with median strain lifespan in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep44620"}], "href": "https://doi.org/10.1038/srep44620"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28304372"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28304372"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Júlia Rodríguez-Comas, Alba Moreno-Asso, Juan Moreno-Vedia, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-708 represses hepatic stellate cells activation and proliferation by targeting ZEB1 through Wnt/β-catenin pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pharmacol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejphar.2020.172927"}], "href": "https://doi.org/10.1016/j.ejphar.2020.172927"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31962101"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31962101"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wei Zhang, Sheng-Yu Cui, Hong Yi, et al. 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