Abstract:Circular RNAs (circRNAs) exhibit a wide range of physiological and pathological activities. To uncover their role in hepatic steatosis, we investigated the expression profile of circRNAs in HepG2-based hepatic steatosis induced by high-fat stimulation. Differentially expressed circRNAs were subjected to validation using QPCR and functional analyses using principal component analysis, hierarchical clustering, target prediction, gene ontology (GO), and pathway annotation, respectively. Bioinformatic integration … Show more
“…CircRNAs are an evolutionarily conserved class of non-coding RNAs [29] which were reported to be remarkably enriched in the nervous system [30] and play roles in brain function [21,31,32]. To identify key circRNAs that correlated with Nrf2-mediated neuroprotection in the brain, DEcircRNAs in the substantia nigra and corpus striatum tissues between Nrf2 (-/-) and Nrf2 (+/+) mice were identified by microarray and bioinformatics analysis.…”
Background/Aims: The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a protective role in both acute neuronal damage and chronic neurodegeneration-related oxidative stress. Circular RNAs (circRNAs) are involved with various diseases in the central nervous system (CNS). This study aimed to identify the key circRNAs involved in Nrf2-neuroprotection against oxidative stress. Methods: The differentially expressed circRNAs (DEcircRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice were identified by microarray analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was then used to validate the expression of selected DEcircRNAs in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice. Based on our previous microarray analysis of the differentially expressed mRNAs (DEmRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice, the DEcircRNA-miRNA-DEmRNA interaction network was constructed. Functional annotation of DEmRNAs that shared the same binding miRNAs with DEcircRNAs was performed using gene ontology (GO) and pathway analyses. Results: A total of 65 and 150 significant DEcircRNAs were obtained in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, respectively, and seventeen shared DEcircRNAs were found in both these two tissues. The qRT-PCR results were generally consistent with the microarray results. The DEcircRNA-miRNA-DEmRNA interaction network and pathway analysis indicated that mmu_circRNA_34132, mmu_circRNA_017077 and mmu-circRNA-015216 might be involved with Nrf2-mediated neuroprotection against oxidative stress. Mmu_circRNA_015216 and mmu_circRNA_017077 might play roles in the Nrf2-related transcriptional misregulation and Nrf2-mediated processes of rheumatoid arthritis, respectively. In addition to these two processes, mmu_circRNA_34132 may be a potential regulator of Nrf2-mediated protection for diabetes mellitus and Nrf2-mediated defence against ROS in hearts. Conclusion: In conclusion, our study identified the key DEcircRNAs in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, which might provide new clues for further exploring the mechanism of Nrf2-mediated neuroprotection against oxidative stress and other Nrf2-mediated processes.
“…CircRNAs are an evolutionarily conserved class of non-coding RNAs [29] which were reported to be remarkably enriched in the nervous system [30] and play roles in brain function [21,31,32]. To identify key circRNAs that correlated with Nrf2-mediated neuroprotection in the brain, DEcircRNAs in the substantia nigra and corpus striatum tissues between Nrf2 (-/-) and Nrf2 (+/+) mice were identified by microarray and bioinformatics analysis.…”
Background/Aims: The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a protective role in both acute neuronal damage and chronic neurodegeneration-related oxidative stress. Circular RNAs (circRNAs) are involved with various diseases in the central nervous system (CNS). This study aimed to identify the key circRNAs involved in Nrf2-neuroprotection against oxidative stress. Methods: The differentially expressed circRNAs (DEcircRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice were identified by microarray analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was then used to validate the expression of selected DEcircRNAs in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice. Based on our previous microarray analysis of the differentially expressed mRNAs (DEmRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice, the DEcircRNA-miRNA-DEmRNA interaction network was constructed. Functional annotation of DEmRNAs that shared the same binding miRNAs with DEcircRNAs was performed using gene ontology (GO) and pathway analyses. Results: A total of 65 and 150 significant DEcircRNAs were obtained in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, respectively, and seventeen shared DEcircRNAs were found in both these two tissues. The qRT-PCR results were generally consistent with the microarray results. The DEcircRNA-miRNA-DEmRNA interaction network and pathway analysis indicated that mmu_circRNA_34132, mmu_circRNA_017077 and mmu-circRNA-015216 might be involved with Nrf2-mediated neuroprotection against oxidative stress. Mmu_circRNA_015216 and mmu_circRNA_017077 might play roles in the Nrf2-related transcriptional misregulation and Nrf2-mediated processes of rheumatoid arthritis, respectively. In addition to these two processes, mmu_circRNA_34132 may be a potential regulator of Nrf2-mediated protection for diabetes mellitus and Nrf2-mediated defence against ROS in hearts. Conclusion: In conclusion, our study identified the key DEcircRNAs in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, which might provide new clues for further exploring the mechanism of Nrf2-mediated neuroprotection against oxidative stress and other Nrf2-mediated processes.
“…Previous studies have also indicated the close relationship between circRNAs with hepatic steatosis and NASH, and circRNAs can regulate the cancer cell growth, proliferation, migration and invasion. Guo et al [3] have reported the dysregulation of circRNAs is related to the hepatic steatosis. To date, not many researchers have paid su cient attention to the important role of circRNAs in NAFLD.…”
Section: Discussionmentioning
confidence: 99%
“…Recently, the occurrence of NAFLD has increased at an alarming rate with the rapid growth of obesity in the population. There is growing evidence that NAFLD can be caused by multiple factors, including lipid accumulation in liver, mitochondrial dysfunction, a high fat diet, insulin resistance and genetic factors [3]. Although the underlying mechanism of NAFLD has not been completely explained, recent researches have suggested to nd out potential biomarkers that might be able to do early prediction and diagnosis for patients with NAFLD.…”
Background: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the hepatic cholesterol accumulation. Circular RNA (circRNA), one of noncoding RNA, involves in many liver diseases progression. However, no recent studies on circRNA expression profiles in NAFLD have been reported previously.Methods: A NAFLD mouse model was constructed by providing high-fat diet (HFD) for 32 weeks. The circRNAs expression profile in normal mice and NAFLD mice were determined using high-output RNA sequencing method and bioinformatics methods, while the differentially expressed circRNAs were confirmed using Sanger sequencing and qRT-PCR. The circRNA-miRNA network was also predicted. The biological functions of circRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).Results: The results demonstrated the successful construction of NAFLD mice model by immunohistology and serology assay. In total, 93 dysregulated circRNAs were observed, including 57 upregulated circRNAs and 36 downregulated circRNAs, in the NAFLD group. The circRNA-miRNA network revealed the complex interaction between circRNAs and its potential miRNA targets in NAFLD. The characteristic of tissue-specific expression in circRNA was demonstrated. The differentially expressed circRNAs with important biological function were also annotated using GO and KEGG. Both DDAH1 and VAV3 genes were found to be associated with the NAFLD development.Conclusions: Taken together, this study demonstrated the circRNAs expression profile and features in NAFLD, which may provide potential biological markers for the pathogenesis of NAFLD.
“…Most of these differential circRNAs (hsa_circRNA_070616, hsa_circRNA_103716, hsa_circRNA_104854, hsa_circRNA_004183, hsa_circRNA_044353) are reported expressed in the mammalian brain [24]. Li et al [25] have reported that hsa_circRNA_004183 play an important regulatory role in hepatic steatosis, but there is no report about the detailed mechanism. Hsa_circRNA_070616 and hsa_circRNA_103716 are selected for further analysis because they are both predicted as sponge of hsa-miR-574-5p.…”
Background/Aims: CircRNAs play an important role in regulating gene expression and the specific role of circRNAs in the pathogenesis of repeated implantation failure remains unclear. The aim of this study is to assess the differentially expressed circRNAs in patients with repeated implantation failure. Methods: We screened circRNA expression profiles in endometrial biopsies taken from six women with repeated implantation failure and control group using circRNA microarray. Bioinformatic analyses were applied to study these differentially expressed circRNAs. Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm these results. Results: The data from circRNA microarrays clearly revealed that 856 unique circRNAs were significantly altered (p<0.05). The up-regulated expression of hsa_circRNA_070616, hsa_circRNA_103716, hsa_circRNA_104001, hsa_circRNA_104854 and the down-regulated expression of hsa_circRNA_004183, hsa_circRNA_044353, hsa_circRNA_404686 were further validated by qRT-PCR. Conclusion: this study demonstrates that a number of circRNAs were differentially expressed in patients with repeated implantation failure compared with normal controls and may offer novel molecular candidates for diagnosis and clinical treatment of embryo implantation failures.
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