{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR-3188 exhibits diverse functions in cancer biology. In nasopharyngeal carcinoma, it acts as a tumor suppressor by directly targeting mTOR to disrupt the p-PI3K/p-AKT/c-JUN signaling cascade, thereby reducing cell cycle progression and proliferation, enhancing chemosensitivity, and ultimately prolonging survival in preclinical models. In hepatocellular carcinoma, in contrast, its overexpression promotes cell viability and proliferation while inhibiting apoptosis through targeting CXCL14. Furthermore, emerging evidence from head and neck cancer studies suggests that alterations in miR-3188 levels within cancer‐associated fibroblast exosomes could contribute to malignant transformation."}, {"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 vascular and metabolic contexts, miR-3188 plays a regulatory role in endothelial and macrophage function. Its downregulation in oxidized LDL‐treated macrophages is associated with enhanced cell injury and inflammation via upregulation of its target ELK4 and subsequent activation of the RhoA/ROCK pathway, suggesting a protective effect when overexpressed. In patients with type 2 diabetes, a functional polymorphism in miR-3188 (rs7247237-C>T) impairs nitric oxide production in endothelial cells by modulating AKT/eNOS signaling through altered expression of genes such as gstm1 and trib3, thereby influencing the risk of 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": "\nBeyond its roles in cancer and vascular biology, miR-3188 is implicated in immune regulation and viral pathogenesis. In Epstein–Barr virus-infected B cells, reduced expression of miR-3188—modulated by a protective allele at an MS risk locus—suggests that it may be involved in the dysregulation of B cell miRNA networks that contribute to multiple sclerosis pathogenesis. In hepatitis B infection, overexpression of miR-3188 suppresses viral transcription by targeting the host protein Bcl-2, highlighting its potential to modulate HBV cccDNA transcription."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the reproductive system, miR-3188 contributes to ovarian dysfunction in polycystic ovary syndrome (PCOS) by promoting the proliferation and survival of granulosa cells. Elevated levels of miR-3188 in PCOS patients lead to enhanced cell cycle progression, with increased cyclin D1 and decreased p21 expression, partly through direct targeting and downregulation of KCNA5."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mengyang Zhao, Rongcheng Luo, Yiyi Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR-p-PI3K/AKT-c-JUN."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms11309"}], "href": "https://doi.org/10.1038/ncomms11309"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27095304"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27095304"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xiaoning Wang, Xing Qin, Ming Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of exosomal miR-3188 in cancer-associated fibroblasts contributes to HNC progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-019-1144-9"}], "href": "https://doi.org/10.1186/s13046-019-1144-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30961650"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30961650"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jianguo Xu, Fei Liu, Zhenglin Xia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-3188 regulates the proliferation and apoptosis of hepatocellular carcinoma cells by targeting "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "CXCL14"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomark Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2217/bmm-2020-0685"}], "href": "https://doi.org/10.2217/bmm-2020-0685"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34704819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34704819"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Na Li, Jinghong Chen, Jingru Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-3188 targets ETS-domain protein 4 and participates in RhoA/ROCK pathway to regulate the development of atherosclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmazie (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1691/ph.2017.7686"}], "href": "https://doi.org/10.1691/ph.2017.7686"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29442044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29442044"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Bin Wu, Guojing Liu, Fazhong He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-3188 (rs7247237-C>T) Single-Nucleotide Polymorphism Is Associated With the Incidence of Vascular Complications in Chinese Patients With Type 2 Diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cardiovasc Pharmacol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/FJC.0000000000000681"}], "href": "https://doi.org/10.1097/FJC.0000000000000681"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31274844"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31274844"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ali Afrasiabi, Nicole L Fewings, Stephen D Schibeci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Interaction of Human and "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Epstein-Barr Virus"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " miRNAs with Multiple Sclerosis Risk Loci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms22062927"}], "href": "https://doi.org/10.3390/ijms22062927"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33805769"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33805769"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Shijie Wang, Ying Xie, Fufei Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-3188 inhibits hepatitis B virus transcription by targeting Bcl-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Virol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00705-024-05992-x"}], "href": "https://doi.org/10.1007/s00705-024-05992-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38565755"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38565755"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Shan Zhou, Liang Xia, Yuanyuan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-3188 Regulates proliferation and apoptosis of granulosa cells by targeting KCNA5 in the polycystic ovary syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Biochim Pol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18388/abp.2020_5441"}], "href": "https://doi.org/10.18388/abp.2020_5441"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33533580"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33533580"}]}]}]}