MicroRNA-103a-3p controls proliferation and osteogenic differentiation of human adipose tissue-derived stromal cells

Abstract

The elucidation of the molecular mechanisms underlying the differentiation and proliferation of human adipose tissue-derived stromal cells (hADSCs) represents a critical step in the development of hADSCs-based cellular therapies. To examine the role of the microRNA-103a-3p (miR-103a-3p) in hADSCs functions, miR-103a-3p mimics were transfected into hADSCs in order to overexpress miR-103a-3p. Osteogenic differentiation was induced for 14 days in an osetogenic differentiation medium and assessed by using an Alizarin Red S stain. The regulation of the expression of CDK6 (cyclin-dependent kinase 6), a predicted target of miR-103a-3p, was determined by western blot, real-time PCR and luciferase reporter assays. Overexpression of miR-103a-3p inhibited the proliferation and osteogenic differentiation of hADSCs. In addition, it downregulated protein and mRNA levels of predicted target of miR-103a-3p (CDK6 and DICER1). In contrast, inhibition of miR-103a-3p with 2′O methyl antisense RNA increased the proliferation and osteogenic differentiation of hADSCs. The luciferase reporter activity of the construct containing the miR-103a-3p target site within the CDK6 and DICER1 3′-untranslated regions was lower in miR-103a-3p-transfected hADSCs than in control miRNA-transfected hADSCs. RNA interference-mediated downregulation of CDK6 and DICER1 in hADSCs inhibited their proliferation and osteogenic differentiation. The results of the current study indicate that miR-103a-3p regulates the osteogenic differentiation of hADSCs and proliferation of hADSCs by direct targeting of CDK6 and DICER1 partly. These findings further elucidate the molecular mechanisms governing the differentiation and proliferation of hADSCs.

Effects of Acute Aerobic Exercise on Rats Serum Extracellular Vesicles Diameter, Concentration and Small RNAs Content

“…In addition, some of the plasma miRNAs (miR-146a and miR-20a) positively correlated with peak exercise capacity and cardiorespiratory fitness ( Colombo et al, 2014 ). Our group demonstrated in a previous report that muscle specific miRNAs (miR-1, 133a and 206) increased in plasma immediately after a half marathon in five trained young male runners ( Da Sol Kim et al, 2015 ). Another study focused on the impact of a single bout of high-intensity resistance exercise (RE) on skeletal muscle and circulatory miRNAs, simultaneously.…”

“…The field of exercise science also took a keen interest. Circulating cell free RNAs, mainly microRNAs, have been investigated as biomarkers in different models of exercise intervention, such as aerobic training ( Colombo et al, 2014 ), power training ( Contarteze et al, 2008 ) and in competitive races ( Da Sol Kim et al, 2015 ; D’Souza et al, 2017 ). It is not yet possible to call a set of circulating microRNAs that would be called more prevalent or related to specific aspects of exercise ( Frühbeis et al, 2015 ).…”

Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma

“…Previous studies showed that CDK6 along with Cyclin D steers cell cycle process from G 1 to S phase via the phosphorylation and inactivation of the RB1 29 . Also, it has been reported that miR-103a-3p and miR-107 could negatively regulate CDK6 and other oncogenic factors 30 31 . Our experiment results agreed with these findings.…”

MICROmanagement of Runx2 Function in Skeletal Cells

“…These findings suggest that miR-103a is a mechanosensitive miRNA that targets Runx2 to inhibit osteoblast differentiation [47] . Additional studies indicate that miR-103a-3p regulates the growth and osteogenic differentiation of human derived stromal cells (hADSCs) by direct targeting of CDK6 and DICER1 partly [48] .…”