{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR-3189 is a primate‐specific microRNA embedded within the intron of the growth differentiation factor 15 (GDF15) gene and is tightly regulated by p53. Its function as a tumor suppressor is evidenced by the observation that antagonizing miR-3189 leads to increased cell proliferation and reduced sensitivity to DNA damage-induced apoptosis, while its overexpression triggers potent apoptotic pathways via both p53‐dependent and independent mechanisms. These findings indicate that miR-3189 inhibits a broad set of genes involved in cell cycle control and cell survival, ultimately contributing to the upregulation of p53 effectors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn tumor contexts such as glioblastoma and gastric cancer, miR-3189-3p expression is markedly downregulated relative to normal tissue. Restoration of miR-3189-3p expression in glioblastoma cells has been shown to inhibit cell proliferation and migration by directly targeting oncogenic regulators including the splicing factor SF3B2 and the guanine nucleotide exchange factor p63RhoGEF, while in gastric cancer cells its overexpression suppresses proliferation and migration through downregulation of CFL2. These results underscore the microRNA’s pivotal role in restraining tumor aggressiveness by counteracting key growth-promoting pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent studies have further implicated epigenetic mechanisms in the regulation of miR-3189 expression in glioblastoma. miR-3189-3p has been identified as a target of polycomb repressive complex-2 (PRC2)-mediated H3K27me3 modification, leading to its reduced expression in glioblastoma patients. This epigenetic silencing results in the derepression of COL6A2, a member of the Collagen VI family that, when overexpressed, promotes epithelial-mesenchymal transition and enhances tumor malignancy. Targeting the H3K27me3/miR-3189-3p/COL6A2 regulatory axis therefore represents a promising therapeutic strategy in glioma treatment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Duane Jeansonne, Mariacristina DeLuca, Luis Marrero, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anti-tumoral effects of miR-3189-3p in glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.633081"}], "href": "https://doi.org/10.1074/jbc.M114.633081"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25645911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25645911"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "M F Jones, X Ling Li, M Subramanian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Growth differentiation factor-15 encodes a novel microRNA 3189 that functions as a potent regulator of cell death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2015.9"}], "href": "https://doi.org/10.1038/cdd.2015.9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25698447"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25698447"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yue Bian, Junfu Guo, Linlin Qiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-3189-3p Mimics Enhance the Effects of S100A4 siRNA on the Inhibition of Proliferation and Migration of Gastric Cancer Cells by Targeting CFL2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms19010236"}], "href": "https://doi.org/10.3390/ijms19010236"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29342841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29342841"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Vikas Sharma, Omkar Suhas Vinchure, Garima Yadav, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel interplay between PRC2 and miR-3189 regulates epithelial-mesenchymal transition (EMT) via modulating COL6A2 in glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.31326"}], "href": "https://doi.org/10.1002/jcp.31326"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38860406"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38860406"}]}]}]}