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  • Author: Xirong Guo x
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Lingxia Pang, Lianghui You, Chenbo Ji, Chunmei Shi, Ling Chen, Lei Yang, Fangyan Huang, Yahui Zhou, Jun Zhang, Xiaohui Chen and Xirong Guo

Excessive adipocyte differentiation and proliferation are closely associated with the onset of obesity, which has been partially linked to microRNA expression. In previous studies, using miRNA microarray screening, we found that miR-1275 was significantly decreased in human mature adipocytes. In this study, we examined the role of miR-1275 in adipogenesis. Our results indicated that miR-1275 can inhibit the differentiation of human visceral preadipocytes without affecting their proliferation. ELK1, an E-twenty-six (ETS)-domain transcription factor associated with adipocyte differentiation, was strongly suppressed by miR-1275 in human visceral adipocytes. This was demonstrated via a dual-luciferase reporter assay and pointed to ELK1 as a direct target of miR-1275. Furthermore, miR-1275 expression was significantly diminished in the visceral adipose tissue of overweight and obese human subjects accompanied by a negative correlation with body mass index. These results suggest that miR-1275 could play a future role in the management of obesity, as a novel therapeutic target or biomarker.

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Yingdi Yuan, Xin guo Cao, Jiaojiao Hu, Jingyun Li, Dan Shen, Lianghui You, Xianwei Cui, Xing Wang, Yahui Zhou, Yao Gao, Lijun Zhu, Pengfei Xu, Chen-bo Ji, Xirong Guo and Juan Wen

Obesity is a major risk factor for metabolic diseases, while adipocyte differentiation is closely related to obesity occurrence. Long noncoding RNAs (lncRNAs) are a unique class of transcripts in regulation of various biological processes. Using lncRNA microarray, we found lncRNA AC092159.2 was highly expressed in differentiated HPA-v and located ~247bp upstream of the TMEM18, which was associated with BMI and obesity. We aimed to explore the role of AC092159.2 in adipogenesis and the underlying mechanisms. The effects of AC092159.2 gain- and loss-of-function on HPA-v adipogenesis were determined with lentivirus and siRNA mediated cell transduction, respectively. Lipid accumulation was evaluated by oil red O staining; the expression of AC092159.2, TMEM18 and several adipogenesis makers in HPA-v were analyzed by qPCR/western blot. We found the expression of AC092159.2 gradually increased during HPA-v differentiation, and its expression in omental adipose tissue was positively related with BMI among 48 human subjects. Overexpression of AC092159.2 promoted adipocytes differentiation while knockdown of it leaded to an adipogenic defect. Moreover, the expression of AC092159.2 and TMEM18 were positively correlated during adipogenic differentiation. AC092159.2 overexpression boosted TMEM18 expression while AC092159.2 knockdown restrained TMEM18 expression. Further rescue experiments showed that TMEM18 knockdown partially restrained adipogenic differentiation in AC092159.2 overexpressed HPA-v, and adipogenic defect caused by AC092159.2 knockdown could be rescued by TMEM18 overexpression. Luciferase reporter assays revealed that AC092159.2 had a transcriptional activation effect on TMEM18. We concluded that lncRNA AC092159.2 promoted human adipocytes differentiation possibly by regulating TMEM18.