{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent findings have indicated that miR-4488 is a key exosome-derived microRNA with implications in autoimmune muscle disorders. In patients with dermatomyositis complicated by interstitial lung disease and positive for anti-MDA5 antibodies, miR-4488 was found to be differentially expressed in circulating exosomes. Bioinformatic analyses predicted that its target genes—including DExD-box helicase 39B and MDM2—may contribute to the disease pathogenesis, suggesting a role in modulating immune responses and inflammatory pathways in these patients."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "In the context of melanoma, miR-4488 has emerged as an important oncomiR. Studies in BRAF‐mutant melanoma patients revealed that circulating levels of miR-4488 serve as independent predictors of progression-free survival, and its expression—when considered alongside miR-579-3p levels—can accurately forecast patient outcomes prior to targeted therapy. Moreover, miR-4488, along with another oncomiR, has been implicated in the development of acquired drug resistance, making it a potential predictive marker for treatment efficacy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "In pancreatic neuroendocrine neoplasms, miR-4488 plays a pivotal role in shaping the tumor microenvironment. Exosomes released from hypoxic pNEN cells were shown to be enriched with miR-4488, which upon uptake by tumor-associated macrophages, directly targets and suppresses RTN3. This event triggers enhanced fatty acid oxidation and activates the PI3K/AKT/mTOR signaling pathway via FABP5 downregulation, consequently driving M2-like macrophage polarization. Such macrophage reprogramming fosters the formation of a premetastatic niche through MMP2 secretion, thereby promoting tumor metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Danli Zhong, Chanyuan Wu, Dong Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma-Derived Exosomal hsa-miR-4488 and hsa-miR-1228-5p: Novel Biomarkers for Dermatomyositis-Associated Interstitial Lung Disease with Anti-Melanoma Differentiation-Associated Protein 5 Antibody-Positive Subset."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2021/6676107"}], "href": "https://doi.org/10.1155/2021/6676107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34368354"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34368354"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ciro Francesco Ruggiero, Luigi Fattore, Irene Terrenato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a miRNA-based non-invasive predictive biomarker of response to target therapy in BRAF-mutant melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Theranostics (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/thno.77761"}], "href": "https://doi.org/10.7150/thno.77761"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36438490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36438490"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Vittorio Castaldo, Michele Minopoli, Francesca Di Modugno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulated expression of miR-4443 and miR-4488 in drug resistant melanomas promotes migratory and invasive phenotypes through downregulation of intermediate filament nestin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-023-02878-9"}], "href": "https://doi.org/10.1186/s13046-023-02878-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38008717"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38008717"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Feiyu Lu, Mujie Ye, Yikai Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypoxic tumor-derived exosomal miR-4488 induces macrophage M2 polarization to promote liver metastasis of pancreatic neuroendocrine neoplasm through RTN3/FABP5 mediated fatty acid oxidation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.96831"}], "href": "https://doi.org/10.7150/ijbs.96831"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38904015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38904015"}]}]}]}