{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR-3178 has emerged as a tumor‐suppressive microRNA in several human cancers. In triple‐negative breast cancer, miR-3178 is markedly downregulated, with its low expression correlating with poor overall survival; its restoration suppresses cell proliferation, invasion, and migration by inhibiting the epithelial-to-mesenchymal transition via direct targeting of Notch1. Similarly, in hepatocellular carcinoma (HCC) tumor endothelial cells, reduced miR-3178 levels are associated with enhanced proliferation, invasion, migration, and angiogenesis, while overexpression of miR-3178 inhibits these malignant behaviors by downregulating its target, early growth response gene 3 (EGR3). Moreover, in H. pylori-positive gastric tissues, decreased miR-3178 expression coincides with upregulation of TRAF3 and aberrant NF-κB signaling, suggesting an involvement in modulating inflammation-related carcinogenic pathways."}, {"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": "\nMechanistically, miR-3178 exerts its regulatory effects via multiple oncogenic pathways. mTOR signaling has been shown to suppress miR-3178, resulting in the upregulation of CDC6—a key factor in DNA replication licensing that contributes to unchecked cell cycle progression. In addition, treatment with baicalein increases miR-3178 levels in HCC cells, leading to diminished expression of histone deacetylase 10 (HDAC10) and subsequent inactivation of signaling pathways such as AKT/MDM2/p53/Bcl2/Bax and FoxO3α/p27/CDK2/Cyclin E1 that are critical for cell survival and growth. These findings underscore the role of miR-3178 as a pivotal regulator of cell cycle and survival signals in oncogenesis."}, {"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 studies highlight the multifaceted functions of miR-3178 as a suppressor of tumor progression through its direct targeting of key genes involved in metastasis, cell proliferation, and inflammatory signaling. Modulation of miR-3178—either by restoring its diminished expression in cancerous tissues or by counteracting the pathways that suppress it—represents a promising therapeutic strategy across diverse malignant contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wei Li, Shiqiang Shen, Shanmin Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of tumorigenesis and metastasis of hepatocellular carcinoma tumor endothelial cells by microRNA-3178 and underlying mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2015.07.057"}], "href": "https://doi.org/10.1016/j.bbrc.2015.07.057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26182877"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26182877"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Meijuan Zou, Fang Wang, Aiqin Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-3178 ameliorates inflammation and gastric carcinogenesis promoted by Helicobacter pylori new toxin, Tip-α, by targeting TRAF3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Helicobacter (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/hel.12348"}], "href": "https://doi.org/10.1111/hel.12348"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27493095"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27493095"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Peng Kong, Lie Chen, Muxin Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-3178 inhibits cell proliferation and metastasis by targeting Notch1 in triple-negative breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-1091-y"}], "href": "https://doi.org/10.1038/s41419-018-1091-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30333478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30333478"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xianjin Wu, Shenghua Li, Xing Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "mTOR Signaling Upregulates CDC6 via Suppressing miR-3178 and Promotes the Loading of DNA Replication Helicase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-46052-8"}], "href": "https://doi.org/10.1038/s41598-019-46052-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31285446"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31285446"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Junan Qi, Jun Li, Beibei Bie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-3,178 contributes to the therapeutic action of baicalein against hepatocellular carcinoma cells via modulating HDAC10."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Phytother Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ptr.7613"}], "href": "https://doi.org/10.1002/ptr.7613"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36070933"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36070933"}]}]}]}