{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐4739 (miR‐4739) has emerged as a critical regulator of cell fate decisions in bone marrow‐derived mesenchymal stem cells. In highly osteogenic cells, lower endogenous levels of miR‐4739 correlate with enhanced osteoblastic differentiation, whereas its overexpression targets LRP3, thereby shifting differentiation toward adipogenic lineages. Moreover, in the context of osteoporosis, elevated miR‐4739 levels impair cell viability and osteoblast formation by directly repressing DLX3 expression. This microRNA is also intricately involved in the regulatory network mediated by circular RNA hsa_circ_0006766, which acts as a sponge for miR‐4739 to relieve its inhibition of Notch2, ultimately influencing osteogenic commitment."}, {"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": "\nIn addition to its role in bone metabolism, miR‐4739 is implicated in other disease settings. In prostate cancer, miR‐4739 is notably downregulated as it becomes sequestered by the oncogenic lncRNA VPS9D1‐AS1 along with MEF2D, a mechanism that upregulates MEF2D and promotes tumor progression. Furthermore, elevated plasma levels of miR‐4739 have been independently associated with critical limb ischemia in patients with type 2 diabetes mellitus, underscoring its potential utility as a noninvasive diagnostic biomarker and therapeutic target in vascular complications."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings reveal that miR‐4739 exerts multifaceted functions across diverse biological contexts—modulating mesenchymal stem cell lineage commitment, influencing osteoblast differentiation, and contributing to both oncogenic processes and vascular pathologies. Such diverse regulatory roles highlight miR‐4739 as a promising candidate for miRNA‐based therapeutics in regenerative medicine, oncology, and diabetic vascular disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mona Elsafadi, Muthurangan Manikandan, Nehad M Alajez, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA Hsa_circ_0006766 targets microRNA miR-4739 to regulate osteogenic differentiation of human bone marrow mesenchymal stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.1967712"}], "href": "https://doi.org/10.1080/21655979.2021.1967712"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34524066"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34524066"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ding Li, Qi Yuan, Liang Xiong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The miR-4739/DLX3 Axis Modulates Bone Marrow-Derived Mesenchymal Stem Cell (BMSC) Osteogenesis Affecting Osteoporosis Progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Endocrinol (Lausanne) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fendo.2021.703167"}], "href": "https://doi.org/10.3389/fendo.2021.703167"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34925225"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34925225"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ju-Yi Li, Biao Cheng, Xiu-Fang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circulating MicroRNA-4739 May Be a Potential Biomarker of Critical Limb Ischemia in Patients with Diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2018/4232794"}], "href": "https://doi.org/10.1155/2018/4232794"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30539011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30539011"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xiaobin Wang, Qiangjun Chen, Xi Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZEB1 activated-VPS9D1-AS1 promotes the tumorigenesis and progression of prostate cancer by sponging miR-4739 to upregulate MEF2D."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2019.109557"}], "href": "https://doi.org/10.1016/j.biopha.2019.109557"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31918265"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31918265"}]}]}]}