Emerging studies indicated that both long noncoding RNAs and micro-RNAs play crucial roles in the mediation of adipogenesis, which is closely linked to obesity-related diseases. However, the mechanisms of lncRNA-miRNAs coregulating in adipogenesis are still largely unknown. In this study, we determined that lncRNA growth arrest-specific 5 (GAS5) presented an opposite expression pattern with miR-21a-5p in 3T3-L1 adipocytes development. To explore the role of GAS5 in adipogenesis, pcDNA3.1-GAS5 expression vectors and GAS5-siRNAs were used to perform GAS5 overexpression and knockdown, respectively. Ectopic expression of GAS5 dramatically reduced miR-21a-5p level and suppressed the proliferation of 3T3-L1 preadipocytes, while silencing GAS5 slightly increased miR-21a-5p expression but had no significant influence on the cell viability. In addition, overexpression of GAS5 remarkably decreased the mRNA and protein levels of adipogenic marker genes, and resulted in a notable reduction of lipid accumulation. In contrast, overexpressing miR-21a-5p significantly facilitated differentiation of 3T3-L1 cells. By target gene prediction and luciferase reporter assay, we suggested that GAS5 might indirectly improve the expression of phosphatase and tensin homolog (PTEN) by repressing miR-21a-5p in a miRNA-based regulatory mechanism. Together, GAS5 plays a suppressive role in 3T3-L1 cells adipogenesis, which further highlights the importance of lncRNAs in adipogenesis.
Keywords: 3T3-L1 cells; GAS5; PTEN; adipogenesis; miR-21a-5p.