MiR-137 Controls Proliferation and Differentiation of Human Adipose Tissue Stromal Cells

Abstract

Background/Aims: Demonstrating the molecular mechanisms of human adipose tissue-derived mesenchymal stem cells (hADSCs) differentiation and proliferation could develop hADSCs-based cell therapy. Methods: The microRNA-137 (miR-137) and cell division control protein 42 homolog (CDC42) levels were regulated by oligonucleotides transfection. The adipogenic differentiation was induced for 10 days in an adipogenic medium and assessed by using an Oil Red O stain. The regulation of miR-137 on CDC42 expression was determined by western blot, real-time PCR and luciferase reporter assay. Results: We confirmed the roles of miR-137 on hADSCs proliferation and adipogenic differentiation. We showed that overexpression of miR-137 inhibited both hADSCs proliferation and adipogenic differentiation. Overexpression of miR-137 also downregulated protein and mRNA levels of CDC42, a predicted target of miR-137. In contrast, inhibition of miR-137 with 2'-O-methyl antisense RNA increased proliferation and adipogenic differentiation in hADSCs. Luciferase reporter activity in the miR-137 target site within the CDC42 3'UTR was lower in miR-137-transfected hADSCs than in control miRNA-transfected hADSCs. RNA interference-mediated downregulation of CDC42 in hADSCs inhibited their proliferation and adipogenic differentiation. Conclusion: Our results indicate that miR-137 regulates hADSCs adipogenic differentiation and proliferation by directly targeting CDC42. These findings improve our knowledge of the molecular mechanisms governing hADSCs differentiation and proliferation.