miR-410-3P inhibits adipocyte differentiation by targeting IRS-1 in cancer-associated cachexia patients

miR-410-3P 通过靶向 IRS-1 抑制癌症相关恶病质患者的脂肪细胞分化

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作者:Diya Sun #, Zuoyou Ding #, Lei Shen, Fan Yang, Jun Han, Guohao Wu

Conclusions

The expression of miR-410-3p was higher in subcutaneous adipose tissues and serum exosomes of CAC patients, which significantly inhibits adipogenesis and lipid accumulation. The study shows that miR-410-3p could downregulate IRS-1 and downstream adipose differentiation factors including C/EBP-a and PPAR-γ by targeting 3' noncoding region.

Methods

In this study, miRNA sequencing was firstly used to identify differentially expressed miRNAs related to CAL and the reliability of the conclusions was verified in large population samples. Furthermore, functional experiments were performed by up and down regulating miR-410-3p in adipocytes. The binding of miR-410-3p to Insulin Receptor Substrate 1 (IRS-1) was verified by Luciferase reporter assay and functional experiments of IRS-1 were performed in adipocytes. Finally, the expression of miR-410-3p in serum exosomes was detected.

Results

miR-410-3p was selected as differentially expressed miRNA through screening and validation. Adipogenesis was suppressed in miR-410-3p upregulation experiment and increased in downregulation experiment. Luciferase reporter assay showed that miR-410-3p binds to 3' non-coding region of IRS-1 and represses its expression and ultimately inhibits adipogenesis. miR-410-3p was highly expressed in serum exosomes of CAC patients, which was consistent with results in adipose tissue. Conclusions: The expression of miR-410-3p was higher in subcutaneous adipose tissues and serum exosomes of CAC patients, which significantly inhibits adipogenesis and lipid accumulation. The study shows that miR-410-3p could downregulate IRS-1 and downstream adipose differentiation factors including C/EBP-a and PPAR-γ by targeting 3' noncoding region.

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