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      Relationships of circular RNA with diabetes and depression

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          Abstract

          Type 2 diabetes mellitus (T2DM) is closely related to depression; however, the exact molecular mechnisms of this association are unknown. Here, we investigated whether circular RNAs (circRNAs) in the blood are related to the occurrence of depression in patients with T2DM. Fourteen patients with T2DM and depressive symptoms, as assessed by the Self-Rating Depression Scale, were included in this study. Cutoff points of 44 (total coarse points) and 55 (standard score) were used to define depression. The Patient Health Questionnaire 9 was used for common mental disorders, and a score of 5 or more the cutoff for depression. Microarray assays and quantitative real-time reverse transcription polymerase chain reaction showed that 183 hsa-circRNAs were significantly upregulated, whereas 64 were downregulated in the T2DM with depression group ( p < 0.05) compared with that in the T2DM group. Differentially expressed hsa-circRNAs could interact with microRNAs to target mRNA expression. KEGG pathway analysis predicted that upregulation of hsa-circRNA_003251, hsa-circRNA_015115, hsa-circRNA_100918, and hsa_circRNA_001520 may participate in the thyroid hormone, Wnt, ErbB, and mitogen-activated protein kinase signalling pathways. We speculate that differentially expressed hsa-circRNAs could help us to clarify the pathogenesis of depression in patients with T2DM and could represent novel molecular targets for clinical diagnosis and therapy.

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          miR-761 regulates the mitochondrial network by targeting mitochondrial fission factor.

          Mitochondria are dynamic organelles that constantly undergo fission and fusion. The balance between fission and fusion determines the fate of the cell. In this study, we show that mitochondrial fission factor (MFF) is upregulated upon hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury. Knockdown of MFF attenuated hydrogen peroxide- and I/R injury-induced cardiomyocyte apoptosis and myocardial infarction. We found that MFF is a direct target of miR-761, and miR-761 inhibits mitochondrial fission and cardiomyocyte apoptosis by repressing MFF. This study reveals a novel model of mitochondrial fission regulation, which is composed of miR-761 and MFF. Modulation of their levels may provide a new approach for tackling apoptosis and myocardial infarction. Copyright © 2013 Elsevier Inc. All rights reserved.
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            The link between long noncoding RNAs and depression.

            The major depressive disorder (MDD) is a relatively common mental disorder from which that hundreds of million people have suffered, leading to displeasing life quality, which is characterized by health damage and even suicidal thoughts. The complicated development and functioning of MDD is still under exploration. Long noncoding RNA (lncRNAs) are highly expressed in the brain, could affect neural stem cell maintenance, neurogenesis and gliogenesis, brain patterning, synaptic and stress responses, and neural plasticity. The dysregulation of certain lncRNAs induces in neurodevelopmental, neurodegenerative and neuroimmunological disorders, primary brain tumors, and psychiatric diseases. Although advances have been made, no fully satisfactory treatments for major depression are available, further investigation is requested. And recently data showed that the expression level of the majority of lncRNAs demonstrated a clear tendency of upregulation, and the certain dysregulated miRNAs and lncRNAs in the MDD have been proved to have a co-synergism mechanism, that is why we speculate lncRNA might get the capability to regulate MDD. Few identified lncRNAs have been deeply studied in detailed experiments up until now, little predictions of their function have been raised, and further researches is calling for discover their signal pathway and related regulatory networks.
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              Molecular Mechanism for Stress-Induced Depression Assessed by Sequencing miRNA and mRNA in Medial Prefrontal Cortex

              Background Major depression is a prevalent mood disorder. Chronic stress is presumably main etiology that leads to the neuron and synapse atrophies in the limbic system. However, the intermediate molecules from stresses to neuronal atrophy remain elusive, which we have studied in the medial prefrontal cortices from depression mice. Methods and Results The mice were treated by the chronic unpredictable mild stress (CUMS) until they expressed depression-like behaviors confirmed by the tests of sucrose preference, forced swimming and Y-maze. High-throughput sequencings of microRNA and mRNA in the medial prefrontal cortices were performed in CUMS-induced depression mice versus control mice to demonstrate the molecular profiles of major depression. In the medial prefrontal cortices of depression-like mice, the levels of mRNAs that translated the proteins for the GABAergic synapses, dopaminergic synapses, myelination, synaptic vesicle cycle and neuronal growth were downregulated. miRNAs of regulating these mRNAs are upregulated. Conclusion The deteriorations of GABAergic and dopaminergic synapses as well as axonal growth are associated with CUMS-induced depression.
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                Author and article information

                Contributors
                piwei001@163.com
                sihuagaopaper@sina.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                4 August 2017
                4 August 2017
                2017
                : 7
                : 7285
                Affiliations
                [1 ]ISNI 0000 0001 1431 9176, GRID grid.24695.3c, Diabetes Research Center, , Beijing University of Chinese Medicine, ; Beijing, 100029 China
                [2 ]ISNI 0000 0001 1431 9176, GRID grid.24695.3c, , Beijing University of Chinese Medicine Third Affiliated Hosiptal, ; Beijing, 100029 China
                [3 ]GRID grid.470210.0, , Hebei Provincial Hospital of Traditional Chinese Medicine, ; Shi Jia Zhuang, 050011 China
                Article
                7931
                10.1038/s41598-017-07931-0
                5544722
                28779132
                c99dbc10-186c-4d3e-976d-5ffce41b0c4f
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 30 March 2017
                : 5 July 2017
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