Transcriptome analysis of long non-coding RNAs reveals NR_015556 lncRNA is a novel regulator for adipocyte differentiation

• Published in: Biochemical and biophysical research communications 2022-04, Vol.601, p.79-85
• Main Authors: Zuo, Changqing, Pan, Yaqiong, Leng, Dan, Chen, Xiuju, Dong, Fanghongniu, Lin, Zhanying, Dai, Zhong, Wang, Zonggui
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Adipocyte differentiation; Adipocytes - metabolism; Adipogenesis - genetics; Animals; beta Catenin - genetics; beta Catenin - metabolism; CCAAT-Enhancer-Binding Protein-alpha - genetics; Cell Differentiation - genetics; Gene Expression Profiling; Mice; NR_015556; PPAR gamma - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Wnt Signaling Pathway - genetics; Wnt10b; β-catenin
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.02.069

Long non-coding RNAs (lncRNAs) have gained extensive attentions due to their significant roles in diverse biological process. However, the potential functions of lncRNAs participation in adipocyte differentiation have not been fully explored. In the present study, we globally profiled lncRNA expression using lncRNA microarray and identified 1745 lncRNA probes with differential expression on day 0 and day 4 post-induction in both C3H10T1/2 mesenchymal stem cells and 3T3-L1 preadipocytes. Furthermore, we showed that stable shRNA knockdown (KD) of NR_015556, a novel lncRNA that was significantly down-regulated in adipocyte differentiation, promoted adipocyte differentiation by increasing the number of lipid droplets and adipocyte markers such as Fabp4, Adipsin and Fasn. Mechanistically, NR_015556 KD attenuated the expression of Wnt signaling components Wnt10b and non-phospho (active) β-catenin, and elevated adipocyte master factors Ppar-γ and C/EBPα levels. Conversely, pharmacological activation of Wnt10b-β-catenin signaling by LiCl suppressed NR_015556 KD-induced enhancement of adipocyte differentiation and Ppar-γ and C/EBPα expression levels. Taken together, these results indicate that down-regulation of NR_015556 promotes adipocyte differentiation through inhibiting Wnt10b-β-catenin signaling pathway and then elevating Ppar-γ and C/EBPα triggered transcriptional cascades. •Long non-coding RNA NR_015556 expression decreased during adipocyte differentiation.•Knockdown of NR_015556 promoted adipocyte differentiation.•Knockdown of NR_015556 inhibited Wnt10b-β-catenin pathway and followed by increasing PPAR-γ and C/EBPα expression.•Small molecule Wnt activator LiCl impaired the enhancement of adipocyte differentiation caused by NR_015556 knockdown.