Long Noncoding RNA ADINR Regulates Adipogenesis by Transcriptionally Activating C/EBPα.
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ABSTRACT:
SUBMITTER: Xiao T
PROVIDER: S-EPMC4649137 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
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Project description:BackgroundActivation of brown adipose tissue (BAT) increases energy expenditure, which makes it an attractive therapeutic strategy for obesity. LncRNAs play an important role in adipocyte differentiation and regulation. Here we assessed the effect of lncRNA XIST on brown preadipocytes differentiation and metabolic regulation.MethodsXIST expression levels were detected in human perirenal (peri-N) and subcutaneous adipose tissues (sub-Q), brown preadipocytes and 3T3-L1 preadipocytes. XIST overexpression and knockdown experiments were performed in brown preadipocytes. XIST overexpression mouse model was established by plasmid injection through tail vein.ResultsIn human adipose tissues, XIST expression was significantly higher in female than in male individuals. In vitro, XIST expression was significantly up-regulated during brown adipocyte differentiation. XIST knockdown inhibited differentiation of brown preadipocytes, while overexpression of XIST promotes brown preadipocytes to fully differentiation. RNA Binding Protein Immunoprecipitation (RIP) experiment revealed that XIST could directly bind to C/EBPα. In vivo, XIST overexpression prevents high-fat diet induced obesity and improves metabolic dysorder in male mice.ConclusionOur results suggest that XIST combats obesity through BAT activation at least partly by combination with transcription factor C/EBPα.
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Project description:ObjectiveCancer-associated cachexia is a devastating pathological disorder characterized by skeletal muscle wasting and fat storage depletion. Circular RNA, a newly discovered class of noncoding RNAs with important roles in regulating lipid metabolism, has not been fully understood in the pathology of cachexia. We aimed to identify circular RNAs that are upregulated in adipose tissues from cachectic patients and explore their function and mechanism in lipid metabolism.MethodsWhole transcriptome RNA sequencing was used to screen for differentially expressed circRNAs. Quantitative reverse transcription PCR was applied to detect the expression level of circPTK2 in adipose tissues. The diagnostic value of circPTK2 was evaluated in adipose tissues from patients with and without cachexia. Then, function experiments in vitro and in vivo were performed to evaluate the effects of circPTK2 on lipolysis and adipogenesis. Mechanistically, luciferase reporter assay, RNA immunoprecipitation, and fluorescent in situ hybridization were performed to confirm the interaction between circPTK2 and miR-182-5p in adipocytes.ResultsWe detected 66 differentially expressed circular RNA candidates and proved that circPTK2 was upregulated in adipose tissues from cachectic patients. Then we identified that circPTK2 was closely related to the pathological process of cachexia and could be used as a diagnostic marker. Mechanistically, circPTK2 bound competitively to miR-182-5p and abrogated the suppression on its target gene JAZF1, which finally led to promotion of lipolysis and inhibition of adipogenesis. In vivo experiments demonstrated that overexpression of circPTK2 inhibited adipogenesis and enhanced lipolysis.ConclusionsOur findings reveal the novel role of circPTK2 in promoting lipolysis and reducing adipogenesis via a ceRNA mechanism and provide a potential diagnostic biomarker and therapeutic target for cancer-associated cachexia.
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Project description:1. Evaluate the diagnostic value of long noncoding RNA (CCAT1) expression by RT-PCR in peripheral blood in colorectal cancer patients versus normal healthy control personal.
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