Abstract
Mesenchymal stem cells (MSCs) are important pluripotent stem cells and a major source of adipocytes in the body. However, the mechanism of adipogenic differentiation has not yet been completely elucidated. In this study, the long noncoding RNA GAS5 was found to be negatively correlated with MSC adipogenic differentiation. GAS5 overexpression negatively regulated adipocyte formation, whereas GAS5 knockdown had the opposite effect. Further mechanistic analyses using luciferase reporter assays revealed that GAS5 regulates the adipogenic differentiation of MSCs by acting as competing endogenous RNA (ceRNA) to sponge miR-18a, which promotes adipogenic differentiation. Mutation of the binding sites for GAS5 in miR-18a abolished the effect of the interaction. The miR-18a mimic and inhibitor reversed the negative regulatory effect of GAS5 on MSCs adipogenic differentiation. In addition, GAS5 inhibited miR-18a, which downregulates connective tissue growth factor (CTGF) expression, to negatively regulate the adipogenic differentiation of MSCs. Taken together, the results show that GAS5 serves as a sponge for miR-18a, inhibiting its capability to suppress CTGF protein translation and ultimately decreasing the adipogenic differentiation of MSCs. GAS5 is an important molecule involved in the adipogenic differentiation of MSCs and may contribute to the functional regulation and clinical applications of MSCs.
Highlights
Mesenchymal stem cells (MSCs) are stem cells with selfrenewal and multi-potential differentiation abilities, which allow them to differentiate into osteogenic, adipogenic, and chondrogenic lineages[1]
The Long noncoding RNAs (lncRNAs) growth arrest-specific transcript 5 (GAS5) negatively correlates with the adipogenic differentiation capacity of MSCs
We analyzed the relative expression of GAS5 and PPAR-γ and observed a negative correlation during the differentiation of MSCs (Fig. 1b), suggesting that GAS5 may exert a negative effect on the differentiation of MSCs into adipocytes
Summary
Mesenchymal stem cells (MSCs) are stem cells with selfrenewal and multi-potential differentiation abilities, which allow them to differentiate into osteogenic, adipogenic, and chondrogenic lineages[1]. Noncoding RNAs are a type of non-protein coding RNA that critically regulate processes determining cell fate. Official journal of the Cell Death Differentiation Association. According to some recent studies, lncRNAs affect MSCs differentiation. HOTAIR impacts MSCs differentiation and is related to senescence-associated DNA methylation[7]. The lncRNA growth arrest-specific transcript 5 (GAS5) is a non-protein coding RNA that is considered a tumor suppressor gene[8,9]. GAS5 exerts crucial effects on biological proliferation and differentiation[10,11,12], but researchers have not determined whether GAS5 affects the adipogenic differentiation of MSCs
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