Super-enhancer-associated miR-1260b coordinates adipogenesis and metabolic programming in human adipose stem cells.

Obesity and its metabolic complications represent a major and growing public health burden, for which effective therapeutic strategies remain limited. Although super-enhancers are recognized as key regulators of cell identity and adipogenesis, the roles of super-enhancer- microRNAs in obesity and adipocyte dysfunction remain insufficiently characterized. Here, we identify miR-1260b as a super-enhancer-associated miRNA that influences human adipogenesis. Analysis of adipose-related datasets from SEdb 2.0 revealed that MIR1260B is consistently linked to a clustered SE region across multiple human adipose tissues. Integrated ATAC-seq and Hi-C analyses demonstrated progressive chromatin opening and dynamic enhancer-promoter interactions between this SE and the MIR1260B promoter during adipogenic differentiation. Functionally, miR-1260b overexpression markedly inhibited adipocyte differentiation of human adipose-derived stem cells. Quantitative proteomic profiling revealed that miR-1260b suppresses adipogenic and lipogenic programmes while activating lipid catabolic pathways. Notably, the MIR1260B-associated SE overlaps with a previously reported diabetes-associated SNP, and external clinical datasets indicate reduced miR-1260b levels in umbilical cord serum from children at increased risk of obesity. Together, these findings suggest that miR-1260b may function as a super-enhancer-associated regulator that inhibits adipogenesis and indicate that SE-informed multi-omics approaches can aid in identifying miRNA regulators relevant to metabolic disorders of obesity.