The novel long noncoding RNA lncRNA-Adi regulates adipogenesis
Yuanwei Chen, Kaide Li, Xiao Zhang, Jinlong Chen, Meisheng Li, Lei Liu
Abstract
Abstract Adipogenesis participates in many physiological and pathological processes, such as obesity and diabetes, and is regulated by a series of precise molecular events. However, the molecules involved in this regulation have not been fully characterized. In this study, we identified a long noncoding (lnc)RNA, lncRNA-Adi, which is highly expressed in adipose tissue-derived stromal cells (ADSCs) that are differentiating into adipocytes. Knockdown of lncRNA-Adi impaired the adipogenic differentiation ability of ADSCs. Moreover, lncRNA-Adi was found to interact with microRNA (miR)-449a to enhance the expression of cyclin-dependent kinase (CDK)6 during adipogenesis. The mechanism by which lncRNA-Adi regulates adipogenesis was determined to involve an lncRNA-Adi-miR-449a interaction that competes with the CDK6 3′ untranslated region to increase CDK6 translation and activate the pRb-E2F1 pathway to promote adipogenesis. These findings provide valuable information and a new study angle to search for therapeutic targets against metabolic disorders such as obesity and diabetes. Significance statement This study found a new lncRNA, which was named lncRNA-Adi, that highly expressed in adipogenic-induced ADSCs. Furthermore, lncRNA-Adi could competitively interact with miR-449a, which protects CDK6 from degradation by miR-449a, to improve CDK6 translation level and activate pRb-E2F1 pathway, which is crucial to cell proliferation in the early stage of adipogenesis, to promote adipogenesis. These findings not only revealed the function and mechanism of lncRNA-Adi in regulating adipogenesis but also, more importantly, could provide valuable information and a new study angle in the future to search for therapeutic target in fighting against metabolic disorders such as obesity and diabetes.