{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent investigations have linked microRNA-548ac (MIR548AC) to immune-mediated disorders, notably multiple sclerosis (MS). MIR548AC is encoded within the first intron of the CD58 gene, and its evolutionary origin traces to a mariner-derived transposable element. Genetic variants such as SNP rs1414273, positioned at the base of the MIR548AC stem-loop, appear to impair recognition by the Drosha/DGCR8 complex, raising the possibility that altered microRNA processing contributes to MS susceptibility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther molecular analysis in blood-derived cells has revealed an intriguing uncoupling of CD58 gene expression and MIR548AC production. Carriers of the risk allele at rs1414273 exhibit reduced levels of CD58 mRNA alongside increased levels of mature MIR548AC, suggesting that impaired Drosha cleavage may lead to a decoupled processing mechanism. Moreover, MIR548AC is implicated in regulating pathways related to inflammatory responses and protein folding/degradation, which could further influence the pathogenic landscape of MS."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in neuroinflammation, MIR548AC has also been demonstrated to act as a functional mediator in hematopoiesis within the context of acute myeloid leukemia (AML). AML-derived extracellular vesicles, enriched with MIR548AC, can transfer the microRNA to CD34+ hematopoietic stem cells, where it targets TRIM28 and activates STAT3 signaling. This cascade ultimately suppresses colony formation, illustrating a novel mechanism by which MIR548AC exerts regulatory control over hematopoietic differentiation and immune cell function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michael Hecker, Brit Fitzner, Jana Blaschke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Susceptibility variants in the CD58 gene locus point to a role of microRNA-548ac in the pathogenesis of multiple sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mutat Res Rev Mutat Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mrrev.2014.10.002"}], "href": "https://doi.org/10.1016/j.mrrev.2014.10.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25795118"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25795118"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Michael Hecker, Nina Boxberger, Nicole Illner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genetic variant associated with multiple sclerosis inversely affects the expression of CD58 and microRNA-548ac from the same gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1007961"}], "href": "https://doi.org/10.1371/journal.pgen.1007961"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30730892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30730892"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Chen Zhao, Yang Zhao, Jiaqi Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acute myeloid leukemia cell-derived extracellular vesicles carrying microRNA-548ac regulate hematopoietic function via the TRIM28/STAT3 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Gene Ther (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41417-021-00378-6"}], "href": "https://doi.org/10.1038/s41417-021-00378-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34453123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34453123"}]}]}]}