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

Area of Science:

• Molecular Biology
• Genetics
• Metabolic Research

Background:

• Obesity and its metabolic complications are significant public health issues with limited therapeutic options.
• Super-enhancers regulate cell identity and adipogenesis, but their associated microRNAs in obesity are poorly understood.

Purpose of the Study:

• To identify super-enhancer-associated microRNAs involved in human adipogenesis and obesity.
• To investigate the role of miR-1260b in adipocyte differentiation and its potential link to metabolic disorders.

Main Methods:

• Analysis of adipose-related datasets (SEdb 2.0) to link MIR1260B to super-enhancers.
• Integrated ATAC-seq and Hi-C analyses to study chromatin dynamics and enhancer-promoter interactions.
• Functional studies involving miR-1260b overexpression in human adipose-derived stem cells and quantitative proteomic profiling.

Main Results:

• miR-1260b was identified as a super-enhancer-associated microRNA influencing human adipogenesis.
• Overexpression of miR-1260b inhibited adipocyte differentiation and suppressed adipogenic/lipogenic programs while activating lipid catabolism.
• Reduced miR-1260b levels were observed in umbilical cord serum of children at high risk for obesity, and its associated super-enhancer overlaps with a diabetes-associated SNP.

Conclusions:

• miR-1260b acts as a super-enhancer-associated regulator that inhibits adipogenesis.
• Super-enhancer-informed multi-omics approaches can identify microRNA regulators relevant to obesity and metabolic disorders.