{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMiR-4306 has emerged as a critical regulator in cancer biology, acting predominantly as a tumor suppressor. In triple‐negative breast cancer, for example, loss of hormone receptors leads to miR-4306 downregulation, which in turn derepresses targets such as SIX1, Cdc42, and VEGFA, thereby promoting cell proliferation, metastasis, and angiogenesis. In oral squamous cell carcinoma, miR-4306 is negatively regulated by the long non-coding RNA LINC00958; its suppression is associated with enhanced AIM2-driven pyroptosis and impaired p53 signaling, which promote cancer cell survival. Similarly, in esophageal squamous cell carcinoma, enforced expression of miR-4306 hampers cell proliferation, migration, invasion, and epithelial–mesenchymal transition by targeting genes such as SIX3, while in osteosarcoma, its regulation via a miR-4306/CEMIP axis suggests a broader role in modulating oncogenic signaling and tumor progression. Additionally, emerging evidence implicates circular RNAs (e.g., AGFG1) in regulating miR-4306 activity in the esophageal tumor context, further broadening its impact in oncogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in oncogenesis, miR-4306 also influences vascular and inflammatory processes. In arteriosclerosis obliterans, miR-4306 has been among the candidate microRNAs screened as potential early biomarkers for disease detection. In coronary artery disease, reduced levels of platelet-derived miR-4306—delivered via microparticles—impair its ability to suppress VEGFA expression, thereby leading to enhanced ERK1/2 and NF-κB signaling and increased migration of macrophages. This regulatory axis is further supported by studies showing that extracellular vesicle-mediated transfer of miR-4306 modulates capillary tubule formation and lipid handling in both endothelial cells and macrophages."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMiR-4306 also plays diverse roles in non-cancerous diseases, notably in neurodegeneration and intervertebral disc pathology. In neuronal cells exposed to manganese toxicity—a model that mimics aspects of Parkinson’s disease—miR-4306 directly targets the 3’ untranslated region of ATP13A2, and its inhibition ameliorates manganese-induced cytotoxicity, suggesting its involvement in neurodegenerative processes. Similarly, in intervertebral disc degeneration, decreased miR-4306 levels correlate with disease severity, while its overexpression in nucleus pulposus cells promotes cell proliferation, extracellular matrix synthesis, and autophagy, concurrently suppressing apoptosis and matrix degradation via regulation of PAK6."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zitong Zhao, Lin Li, Peina Du, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional Downregulation of miR-4306 serves as a New Therapeutic Target for Triple Negative Breast Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Theranostics (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/thno.30701"}], "href": "https://doi.org/10.7150/thno.30701"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30867840"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30867840"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lei Jiang, Wenyu Ge, Yifei Cui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The regulation of long non-coding RNA 00958 (LINC00958) for oral squamous cell carcinoma (OSCC) cells death through absent in melanoma 2 (AIM2) depending on microRNA-4306 and Sirtuin1 (SIRT1) in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.1955561"}], "href": "https://doi.org/10.1080/21655979.2021.1955561"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34384029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34384029"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Chengyuan Yang, Zichan Guo, Zitong Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-4306 Suppresses Proliferation of Esophageal Squamous Cell Carcinoma Cell by Targeting SIX3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biochem Biophys (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12013-021-00994-x"}], "href": "https://doi.org/10.1007/s12013-021-00994-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34021861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34021861"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Y Zhou, T Mu "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA LINC00958 promotes tumor progression through miR-4306/CEMIP axis in osteosarcoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_202104_25727"}], "href": "https://doi.org/10.26355/eurrev_202104_25727"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33928604"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33928604"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Deming Zhang, Changsheng Li, Nitao Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CircAGFG1 acts as a sponge of miR-4306 to stimulate esophageal cancer progression by modulating MAPRE2 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Histochem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.acthis.2021.151776"}], "href": "https://doi.org/10.1016/j.acthis.2021.151776"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34461454"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34461454"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xue-Mei He, Ying-Qiang Zheng, Sheng-Zhi Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered Plasma MicroRNAs as Novel Biomarkers for Arteriosclerosis Obliterans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Atheroscler Thromb (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.5551/jat.30775"}], "href": "https://doi.org/10.5551/jat.30775"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26370316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26370316"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ying Yang, Hui Luo, Si Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Platelet microparticles-containing miR-4306 inhibits human monocyte-derived macrophages migration through VEGFA/ERK1/2/NF-κB signaling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Hypertens (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/10641963.2018.1510941"}], "href": "https://doi.org/10.1080/10641963.2018.1510941"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30183452"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30183452"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ying Yang, Hui Luo, Can Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of capillary tubules and lipid formation in vascular endothelial cells and macrophages via extracellular vesicle-mediated microRNA-4306 transfer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Int Med Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/0300060518809255"}], "href": "https://doi.org/10.1177/0300060518809255"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30477383"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30477383"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Rong He, Xiaoyun Xie, Linyue Lv, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comprehensive investigation of aberrant microRNAs expression in cells culture model of MnCl2-induced neurodegenerative disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2017.03.041"}], "href": "https://doi.org/10.1016/j.bbrc.2017.03.041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28302480"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28302480"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Dongdong Wang, Ji Zhu, Yuanqing Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of the miR-4306/PAK6 axis in degenerative nucleus pulposus cells in human intervertebral disc degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2022.110528"}], "href": "https://doi.org/10.1016/j.cellsig.2022.110528"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36423859"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36423859"}]}]}]}