{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR-5188 functions as an oncogenic microRNA that promotes aggressive tumor behaviors in breast cancer by enhancing cancer stemness, proliferation, metastasis, and chemoresistance. Mechanistically, miR-5188 directly targets the tumor suppressor FOXO1, which under normal conditions interacts with β‑catenin to facilitate its degradation and limit its nuclear accumulation. Through the downregulation of FOXO1, miR-5188 relieves the inhibitory effect on β‑catenin and, thus, stimulates the activation of Wnt target genes, epithelial‐mesenchymal transition (EMT) markers, and key regulators of cancer stem cell properties. Furthermore, miR-5188 potentiates the Wnt/β‑catenin/c‑Jun signaling pathway while c‑Jun in turn upregulates miR-5188 transcription in a positive feedback loop. The involvement of Timeless and Sp1 in this regulatory network further reinforces the oncogenic circuit, and elevated miR-5188 levels are associated with poor patient prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn glioma, miR-5188 exerts analogous tumor-promoting effects by accelerating cell cycle progression (notably, the G1/S transition), enhancing cell proliferation, migration, and invasion, and ultimately shortening survival in glioma-bearing mice. Similar to its role in breast cancer, miR-5188 targets FOXO1 and activates the PI3K/AKT-c‑Jun signaling cascade, establishing a self-amplifying positive feedback loop via direct binding of c‑Jun to the miR-5188 promoter. This axis, augmented by interactions with transcription factor Sp1, drives glioma progression by reinforcing oncogenic signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yujiao Zou, Xian Lin, Junguo Bu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Timeless-Stimulated miR-5188-FOXO1/β-Catenin-c-Jun Feedback Loop Promotes Stemness via Ubiquitination of β-Catenin in Breast Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Ther (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymthe.2019.08.015"}], "href": "https://doi.org/10.1016/j.ymthe.2019.08.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31604679"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31604679"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Renhui Yi, Shaochun Yang, Xian Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-5188 augments glioma growth, migration and invasion through an SP1-modulated FOXO1-PI3K/AKT-c-JUN-positive feedback circuit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.15794"}], "href": "https://doi.org/10.1111/jcmm.15794"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32902145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32902145"}]}]}]}