{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The long non‐coding RNA DNM3OS (Dynamin 3 Opposite Strand) has emerged as a multifunctional regulatory molecule that contributes to diverse biological processes and disease states. In several cancer types, DNM3OS is frequently overexpressed and acts as an oncogenic hub by modulating microRNA (miRNA) function and downstream gene expression. For example, in esophageal squamous cell carcinoma its elevated expression is linked to enhanced radioresistance"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", while in gastric cancer and hepatocellular carcinoma it promotes cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) through ceRNA mechanisms and epigenetic regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In ovarian and cervical cancers, DNM3OS modulates the bioavailability of tumor‐suppressive miRNAs (such as miR‑193a‑3p and miR‑214) to increase the levels of oncogenic effectors like MAP3K3 and other pro‐tumorigenic factors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond oncology, DNM3OS plays important roles in non‐malignant diseases. In osteoarthritis, it functions as a competitive endogenous RNA (ceRNA) that sponges miR‑126, thereby modulating insulin‐like growth factor 1 (IGF1) expression, which in turn impacts chondrocyte proliferation and apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the context of diabetes‐associated vascular complications, DNM3OS is upregulated in macrophages, suggesting a role in inflammatory dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, in cardiac fibrosis, elevated DNM3OS expression potentiates activation of cardiac fibroblasts by modulating the transforming growth factor‑β1/Smad2/3 pathway"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and in skeletal development, proper DNM3OS levels sustain chondrocyte proliferation and bone growth through regulation of nerve growth factor (NGF) signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In neurological disorders, such as Huntington’s disease, DNM3OS participates in a regulatory circuit by sponging miR‑196b‑5p, which leads to altered glyceraldehyde‑3‑phosphate dehydrogenase (GAPDH) expression and contributes to pathogenic aggregate formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In addition, transcription factors like TWIST1 have been shown to induce DNM3OS expression (harboring miR‑199a/214 clusters), thereby integrating it into broader networks that control tumorigenesis and immune evasion in disorders such as Sézary syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Finally, in mesenchymal stem cells undergoing chondrogenic differentiation under hypoxic conditions, modulation of the DNM3OS/miR‑127‑5p/GREM2 axis further underscores its versatile role in regulating cell fate decisions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight DNM3OS as a key regulatory hub that, by acting as a molecular sponge and modulating epigenetic as well as transcriptional programs, governs critical pathways in cancer progression, fibrosis, inflammation, neural degeneration, and skeletal development. Its multifaceted functions, often mediated via its embedded miRNA clusters or through interactions with proteins (e.g., KDM6B, HDAC6), offer promising avenues for targeted therapeutics across a range of human diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hongfang Zhang, Yuhui Hua, Zhenzhen Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cancer-associated Fibroblast-promoted LncRNA "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "DNM3OS"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Confers Radioresistance by Regulating DNA Damage Response in Esophageal Squamous Cell Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-18-0773"}], "href": "https://doi.org/10.1158/1078-0432.CCR-18-0773"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30463848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30463848"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shuchang Wang, Bo Ni, Zizhen Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA DNM3OS promotes tumor progression and EMT in gastric cancer by associating with Snail."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.02.030"}], "href": "https://doi.org/10.1016/j.bbrc.2019.02.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30770102"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30770102"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Wei Wang, Qun Wang, Da-Bing Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor-associated mesenchymal stem cells promote hepatocellular carcinoma metastasis via a DNM3OS/KDM6B/TIAM1 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2021.01.011"}], "href": "https://doi.org/10.1016/j.canlet.2021.01.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33472090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33472090"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lei He, Guolin He "}, {"type": "b", "children": [{"type": "t", "text": "DNM3OS Facilitates Ovarian Cancer Progression by Regulating miR-193a-3p/MAP3K3 Axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Yonsei Med J (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3349/ymj.2021.62.6.535"}], "href": "https://doi.org/10.3349/ymj.2021.62.6.535"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34027641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34027641"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hongjuan Song, Yuan Liu, Hui Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPINT1-AS1 Drives Cervical Cancer Progression via Repressing miR-214 Biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Cell Dev Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fcell.2021.691140"}], "href": "https://doi.org/10.3389/fcell.2021.691140"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34350182"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34350182"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Di Ai, Fang Yu "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA DNM3OS promotes proliferation and inhibits apoptosis through modulating IGF1 expression by sponging MiR-126 in CHON-001 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diagn Pathol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13000-019-0877-2"}], "href": "https://doi.org/10.1186/s13000-019-0877-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31526393"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31526393"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sadhan Das, Marpadga A Reddy, Parijat Senapati, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Diabetes Mellitus-Induced Long Noncoding RNA Dnm3os Regulates Macrophage Functions and Inflammation via Nuclear Mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.117.310663"}], "href": "https://doi.org/10.1161/ATVBAHA.117.310663"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29930005"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29930005"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Qihang Kong, Junteng Zhou, Geer Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[The potential role of long non-coding RNA Dnm3os in the activation of cardiac fibroblasts]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sheng Wu Yi Xue Gong Cheng Xue Za Zhi (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7507/1001-5515.202102021"}], "href": "https://doi.org/10.7507/1001-5515.202102021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34180204"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34180204"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Ting-Ting Yu, Qiu-Fan Xu, Si-Yang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion at an 1q24 locus reveals a critical role of long noncoding RNA DNM3OS in skeletal development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biosci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13578-021-00559-8"}], "href": "https://doi.org/10.1186/s13578-021-00559-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33653390"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33653390"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Xiaoyu Dong, Shuyan Cong "}, {"type": "b", "children": [{"type": "t", "text": "DNM3OS regulates GAPDH expression and influences the molecular pathogenesis of Huntington's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.16838"}], "href": "https://doi.org/10.1111/jcmm.16838"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34369082"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34369082"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jan P Nicolay, Moritz Felcht, Kai Schledzewski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sézary syndrome: old enigmas, new targets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dtsch Dermatol Ges (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/ddg.12900"}], "href": "https://doi.org/10.1111/ddg.12900"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26972187"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26972187"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Xiaozhong Zhou, Wangyang Xu, Yeyang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA DNM3OS regulates GREM2 via miR-127-5p to suppress early chondrogenic differentiation of rat mesenchymal stem cells under hypoxic conditions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s11658-021-00269-6"}], "href": "https://doi.org/10.1186/s11658-021-00269-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34049478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34049478"}]}]}]}