{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that microRNA MIR4638 plays a pivotal role in regulating cancer cell growth and progression. In castration resistant prostate cancer (CRPC), miR-4638-5p is found to be significantly underexpressed compared to androgen dependent prostate cancer. Functional analyses have demonstrated that restoration of miR-4638-5p suppresses androgen-independent growth both in vitro and in vivo by directly targeting Kidins220. This targeting results in decreased activity of the PI3K/AKT pathway as well as a reduction in VEGF‐mediated angiogenesis, suggesting that loss of miR-4638-5p may contribute to the development of castration resistance and increased tumor aggressiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\nSeparately, investigations in metastatic triple-negative breast cancer have identified that TGF‑β1 downregulates miR-4638-3p expression. This downregulation relieves the inhibitory control on ATF3, leading to its increased expression and subsequent activation of pathways that promote tumor cell proliferation, invasion, and bone metastasis. Thus, MIR4638 (via its −3p form) emerges as a critical regulator of metastasis by modulating ATF3 levels and its downstream effectors, indicating its potential as both a biomarker and therapeutic target in metastatic breast cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yang Wang, Ning Shao, Xueying Mao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-4638-5p inhibits castration resistance of prostate cancer through repressing Kidins220 expression and PI3K/AKT pathway activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.10165"}], "href": "https://doi.org/10.18632/oncotarget.10165"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27329728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27329728"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "R L Akshaya, I Saranya, G Margaret Salomi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In vivo validation of the functional role of MicroRNA-4638-3p in breast cancer bone metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-023-05601-5"}], "href": "https://doi.org/10.1007/s00432-023-05601-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38300343"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38300343"}]}]}]}