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The disruption of circadian rhythms caused by long-term shift work can cause metabolic diseases such as obesity. Early growth response 3 (EGR3) is a member of early growth response (EGR) family, which is involved in several cellular responses, had been reported as a circadian rhythm gene in suprachiasmatic nucleus. In this research, EGR3 was found to be widely expressed in the different tissue of human and mice, and downregulated in adipose tissue of obese subjects and high-fat diet mice. Moreover, EGR3 was found negatively regulated by cortisol. In addition, EGR3 is a key negative modulator of hADSCs and 3T3-L1 adipogenesis via regulating HDAC6, which is a downstream target gene of EGR3 and a negative regulator of adipogenesis and lipogenesis. These findings may explain how circadian rhythm disorder induced by shift works can cause obesity. Our study revealed a potential therapeutic target to alleviate metabolic disorders in shift workers and may provide better health guidance to shift workers.
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Purpose: Adipogenesis is one of the major pathways for generating obesity or overweight that can cause a range of metabolic disorders. Circular RNAs (circRNAs), a specific type of RNAs, have a significant influence on metabolic disorders. This study aims to find differentially expressed circRNAs (DECs) during human subcutaneous adipose tissue (SATs) adipogenesis. Patients and Methods: The human adipose tissue-derived stromal cells (hADSCs) were isolated from human SATs (n = 3), and then induced into adipocytes. Total RNAs were extracted from hADSCs and adipocytes, and he DECs were detected using circRNA microarray. The GO and KEGG pathways of DECs were analyzed by bioinformatic methods, and partial DECs were further validated by quantitative polymerase chain reaction (qPCR). Results: Our study detected a total of 1987 DECs, among which, 1134 were found upregulated and 853 were downregulated. GO analysis showed that the upregulated DECs have catalytic activity in intracellular organelle and cytoplasms, whereas downregulated DECs are enriched in organelle lumen, and are involved in positive regulation of developmental process. In addition, pathway results demonstrated that upregulated DECs are involved in platinum drug resistance and cellular senescence, and downregulated DECs are enriched in proteoglycans in cancer and focal adhesion pathway. Two circRNAs, namely has_circ_0001600 and has_circ_0001947 were validated to be significantly upregulated in adipocytes compared to hADSCs. Conclusion: Our study explored DECs between hADSCs derived from SATs and adipocytes, and report that two circRNAs named has_circ_0001600 and has_circ_0001947 might be important factors involved in human adipogenesis, however, the molecular mechanism should be further explored.
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Purpose: Brown adipose tissue (BAT) can rapidly generate heat and improve energy metabolism. Circular RNAs (circRNAs) are cellular endogenous non-coding RNAs, which can regulate the development and progress of different diseases. However, the role of circRNAs in human BAT is not fully understood. Here, we analyzed the differentially expressed circRNAs (DECs) in human BAT, as well as in white adipose tissue (WAT), and identified new biomarkers of BAT. Patients and Methods: Three human BAT and three human subcutaneous WAT samples were selected, and circRNA microarray was performed. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the expression of six circRNAs. Finally, the functional analysis was performed by bioinformatics. Results: Compared to WAT, 152 upregulated circRNAs and 201 downregulated circRNAs were identified in BAT. The DECs were further subjected to GO and KEGG enrichment analysis. Several circRNAs, for example, hsa_circ_0006168, hsa_circ_26337 and hsa_circ_0007507 were found upregulated and hsa_circ_0030162 was found downregulated in human BAT compared to WAT. Conclusion: This study profiles the circRNA expression in human BAT and WAT, and suggests hsa_circ_0006168, hsa_circ_26337, hsa_circ_0007507, and hsa_circ_0030162 as novel biomarkers for human BAT.
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Purpose: Type 2 diabetes mellitus (T2DM) increases the incidence of diabetic nephropathy (DN) and eventually progresses to end-stage renal disease. Circular RNAs (circRNAs) are a class of non-coding RNAs that are promising as diagnostic biomarkers and therapeutic targets for human diseases. The aim of this study was to analyze the differential expression of circRNAs (DECs) in peripheral blood from patients with early type 2 diabetic nephropathy (ET2DN), T2DM and controls, which will facilitate to discover some new biomarkers for ET2DN. Patients and Methods: Twenty ET2DN patients, 20 T2DM patients, and 20 normal controls were included in this study. Blood samples from 3 random subjects of age- and sex-matched patients in each group, respectively, were used to detect circRNA expression profiles by circRNA microarray, and the circRNA expression of remaining subjects was validated by real-time quantitative polymerase chain reaction (qRT-PCR). Further functional assessment was performed by bioinformatic tools. Results: There were 586 DECs in ET2DN vs T2DM group (249 circRNAs were upregulated and 337 circRNAs were downregulated); 176 circRNAs were upregulated and 101 circRNAs were downregulated in T2DM vs control group; 57 circRNAs were upregulated and 5 circRNAs were downregulated in ET2DN vs control group. The functional and pathway enrichment of DECs were analyzed by GO and KEGG. qRT-PCR results revealed that hsa_circ_0001831 and hsa_circ_0000867 were significantly upregulated in ET2DN group compared to both of T2DM and control group. The ROC curve demonstrated that hsa_circ_0001831 and hsa_circ_0000867 have high sensitivity and specificity associated with ET2DN. Conclusion: Our study showed the expression profiles of circRNAs in ET2DN patients and demonstrated that hsa_circ_0001831 and hsa_circ_0000867 can be used as novel diagnostic biomarkers for ET2DN.
