RESUMO
Physiological levels of glucocorticoids (GCs) are required for proper metabolic control, and excessive GC action has been linked to a variety of pandemic metabolic diseases. MicroRNA (miRNA)-19b plays a critical role in the pathogenesis of GC-induced metabolic diseases. This study explored the potential of miRNA-based therapeutics targeting adipose tissue. Our results showed that overexpressed miR-19b in stromal vascular fraction (SVF) cells derived from subcutaneous adipose tissue had the same effects as dexamethasone (DEX) treatment on the inhibition of adipose browning and oxygen consumption rate. The inhibition of miR-19b blocked DEX-mediated suppression of the expression of browning marker genes as well as the oxygen consumption rate in differentiated SVF cells derived from subcutaneous and brown adipose tissue. Overexpressed miR-19b in SVF cells derived from brown adipose tissue had the same effects as DEX treatment on the inhibition of brown adipose differentiation and energy expenditure. Glucocorticoids transcriptionally regulate the expression of miR-19b via a GC receptor-mediated direct DNA binding mechanism. This study confirmed that miR-19b is an essential target for GC-mediated control of adipose tissue browning. It is hoped that the plasticity of the adipose organ can be exploited in the next generation of therapeutic strategies to combat the increasing incidence of metabolic diseases, including obesity and diabetes.
Assuntos
Adipogenia , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Metabolismo Energético , Glucocorticoides/metabolismo , MicroRNAs/metabolismo , Receptores de Glucocorticoides/agonistas , Células 3T3-L1 , Adipogenia/efeitos dos fármacos , Tecido Adiposo Marrom/citologia , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/citologia , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Células Cultivadas , Dexametasona/farmacologia , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Metabolismo Energético/efeitos dos fármacos , Glucocorticoides/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , Mutação , Consumo de Oxigênio/efeitos dos fármacos , Regiões Promotoras Genéticas/efeitos dos fármacos , RNA/antagonistas & inibidores , RNA/metabolismo , Receptores de Glucocorticoides/metabolismo , Células Estromais/citologia , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Gordura Subcutânea/citologia , Gordura Subcutânea/efeitos dos fármacos , Gordura Subcutânea/metabolismoRESUMO
Recent evidence haas indicated that meningioma-associate protein (MAC30) exhibits different expression patterns in various tumors. However, little is known about the value of MAC30 in human squamous cell carcinoma of lung (SQCLC). The purpose of our study was to investigate the expression of MAC30 and to explore its clinical significance in SQCLC patients. A total of 156 Chinese patients diagnosed with SQCLC were selected for this study. The expression of MAC30 in all tissues was confirmed by immunohistochemical staining. Quantitative real-time PCR was performed to analyze MAC30 mRNA expression in 32 cases of SQCLC patients with corresponding non-tumor lung tissues. We observed enhanced mRNA expression of MAC30 in SQCLC as compared to control samples. Further, elevated MAC30 protein expression was strongly associated with poor tumor differentiation, TNM stage, and lymph node metastasis. In addition, we observed that patients with increased MAC30 expression demonstrated poor overall survival. Multivariate analysis explicated that increased MAC30 expression was a valuable independent predictable factor for poor tumor differentiation and short survival in SQCLC patients. Our present study suggests that MAC30 may serve as a biomarker for poor tumor differentiation and outcomes of patients with SQCLC.