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Li Y, Wang YX, Tang XM, Liang P, Chen JJ, Jiang F, Yang Q, Liang YD. Haplotype analysis of long-chain non-coding RNA NONHSAT102891 promoter polymorphisms and depression in Chinese individuals: A case-control association study. World J Psychiatry 2023; 13:1005-1015. [PMID: 38186730 PMCID: PMC10768487 DOI: 10.5498/wjp.v13.i12.1005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 10/13/2023] [Accepted: 11/09/2023] [Indexed: 12/19/2023] Open
Abstract
BACKGROUND Our previous study reported that the single-nucleotide polymorphism (SNP) rs155979 GC in the promoter region of long-chain non-coding RNA (lncRNA) NONHSAT102891 affects depression susceptibility in a Chinese population. AIM To explored associations of two SNPs and haplotypes in the lncRNA NONHSAT102891 promoter region with depression susceptibility in Chinese population. METHODS This this case-control association study was approved by the Ethics Committee of Chengdu Medical College (approval number: 201815). Patient diagnosis was based on DSM-IV criteria. We selected a total of 480 patients with depression and 329 healthy controls with no history of psychopathology, and performed genotyping of two SNPs by extracting peripheral venous blood samples from the subjects. The function of the two lncRNA NONHSAT102891 promoter G/C and A/T haplotypes was detected by dual-luciferase reporter assays of human embryonic kidney 293T transfected cells. RESULTS Stratified analysis of clinical and genotypic characteristics of our cohort showed that the degree of mild depressive episodes associated with the rs6230 TC/CC genotype increased by 1.59 times [TC/CC vs TT: odds ratio (OR) = 1.59, 95% confidence interval (CI): 1.08-2.35, P = 0.019]. The haploid analysis revealed linkage disequilibrium between rs3792747 and rs6230, and the double SNP CG haplotype was more common in the control group compared to case group, indicating that this haplotype significantly reduced the risk of depression (C/G vs T/A: OR = 0.42, 95%CI: 0.21-0.83, P = 0.01). There was no significant difference in the dual-luciferase reporter activity of the G/C and A/T haplotypes compared with the control group (P > 0.05), indicating that the double SNP haplotype has no transcriptional activity. CONCLUSION The rs3792747 and rs6230 CG haplotypes of the lncRNA NONHSA T102891 promoter may be related to a reduced risk of depression in the Han Chinese population.
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Affiliation(s)
- Yue Li
- Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu 610500, Sichuan Province, China
| | - Yi-Xi Wang
- Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu 610500, Sichuan Province, China
| | - Xing-Ming Tang
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Peng Liang
- Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu 610500, Sichuan Province, China
| | - Jing-Jie Chen
- Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu 610500, Sichuan Province, China
| | - Feng Jiang
- Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu 610500, Sichuan Province, China
| | - Qiang Yang
- Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu 610500, Sichuan Province, China
| | - Yun-Dan Liang
- Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu 610500, Sichuan Province, China
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Baruah C, Nath P, Barah P. LncRNAs in neuropsychiatric disorders and computational insights for their prediction. Mol Biol Rep 2022; 49:11515-11534. [PMID: 36097122 DOI: 10.1007/s11033-022-07819-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 07/20/2022] [Accepted: 07/24/2022] [Indexed: 12/06/2022]
Abstract
Long non-coding RNAs (lncRNAs) are 200 nucleotide extended transcripts that do not encode proteins or possess limited coding ability. LncRNAs epigenetically control several biological functions such as gene regulation, transcription, mRNA splicing, protein interaction, and genomic imprinting. Over the years, drastic progress in understanding the role of lncRNAs in diverse biological processes has been made. LncRNAs are reported to show tissue-specific expression patterns suggesting their potential as novel candidate biomarkers for diseases. Among all other non-coding RNAs, lncRNAs are highly expressed within the brain-enriched or brain-specific regions of the neural tissues. They are abundantly expressed in the neocortex and pre-mature frontal regions of the brain. LncRNAs are co-expressed with the protein-coding genes and have a significant role in the evolution of functions of the brain. Any deregulation in the lncRNAs contributes to disruptions in normal brain functions resulting in multiple neurological disorders. Neuropsychiatric disorders such as schizophrenia, bipolar disease, autism spectrum disorders, and anxiety are associated with the abnormal expression and regulation of lncRNAs. This review aims to highlight the understanding of lncRNAs concerning normal brain functions and their deregulation associated with neuropsychiatric disorders. We have also provided a survey on the available computational tools for the prediction of lncRNAs, their protein coding potentials, and sub-cellular locations, along with a section on existing online databases with known lncRNAs, and their interactions with other molecules.
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Affiliation(s)
- Cinmoyee Baruah
- Department of Molecular Biology and Biotechnology, Tezpur University, 784028, Napaam, Sonitpur, Assam, India
| | - Prangan Nath
- Department of Molecular Biology and Biotechnology, Tezpur University, 784028, Napaam, Sonitpur, Assam, India
| | - Pankaj Barah
- Department of Molecular Biology and Biotechnology, Tezpur University, 784028, Napaam, Sonitpur, Assam, India.
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Long Noncoding RNA LINC00473 Ameliorates Depression-Like Behaviors in Female Mice by Acting as a Molecular Sponge to Regulate miR-497-5p/BDNF Axis. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:4244425. [PMID: 36072768 PMCID: PMC9441382 DOI: 10.1155/2022/4244425] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 07/28/2022] [Accepted: 08/08/2022] [Indexed: 11/18/2022]
Abstract
Background. Depression was a common life-threatening psychiatric disorder and occurs more frequently in women than in men. Long noncoding RNAs (lncRNAs), such as LINC00473, had been reported to be involved in the progression of depression. Methods. Chronic unpredictable moderate stress in mice (CUMS) was applied to construct a depression model. Subsequently, RT-qPCR was applied to check the level of LINC00473 and microRNA-497-5p (miR-497-5p) in the hippocampal region of the mice induced by CUMS. CUMS mice were injected with lentiviral vectors of LINC00473 (LV-LINC00473), miR-497-5p inhibitor, short hairpin- (sh-) brain-derived neurotrophic factor (sh-BDNF), or miR-497-5p mimic to evaluate depressive behaviors, including sucrose preference test, forced swim test, elevated plus maze, and tail suspension test. Moreover, the production of hypothalamic neurotransmitters was assessed with the usage of ELISA kits. Dual-luciferase reporter assay, RNA pull-down, and RIP analysis were performed to measure the relationship between miR-497-5p and LINC00473 or BDNF. Further, western blot was employed to determine the protein level of BDNF. Results. We discovered that LINC00473 level was downregulated in the female mice with depression, but not in male mice. Besides, the depressive behaviors induced by CUMS in mice, including the decrease of sucrose preference and time in open arm, as well as the increase of immobility time and swimming resting time were all ameliorated by LINC00473 overexpression. Moreover, the concentration of neurotransmitters was decreased in CUMS-induced mouse hypothalamus, which was blocked by LV-LINC00473 lentiviral vector administration. Mechanistically, LINC00473 directly targeted miR-497-5p. Absence of miR-497-5p revealed the antidepression effects on CUMS-induced mice, and miR-497-5p upregulation could counter the antidepressive impacts of LINC00473 upregulation on CUMS-induced mice. Furthermore, LINC00473 could target miR-497-5p to modulate BDNF level. Knockdown of BDNF could abrogate the improving influences of miR-497-5p suppression on CUMS-induced depression. Conclusions. LINC00473 ameliorated CUMS-caused depression by encouraging BDNF expression via binding to miR-497-5p, which might provide a potential therapeutic target for depression in females.
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Nie K, Liu L, Peng L, Zhang M, Zhang C, Xiao B, Xia Z, Huang W. Effects of Meranzin Hydrate On the LncRNA-miRNA-mRNA Regulatory Network in the Hippocampus of a Rat Model of Depression. J Mol Neurosci 2022; 72:910-922. [PMID: 35099722 DOI: 10.1007/s12031-022-01971-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 01/10/2022] [Indexed: 10/19/2022]
Abstract
Meranzin hydrate (MH) is a frequently used antidepressant drug in China; however it underlying mechanism remains unknown. In this study, we aimed to explore whether MH could ameliorate depression-like behavior in rats by regulating the competitive endogenous RNA (ceRNA) network. We developed a depression-like rat model using an unpredictable chronic mild stress (UCMS) protocol, and the differentially expressed lncRNAs, miRNAs, and mRNAs were identified between the model group and MH group. Then, a ceRNA network responding to MH treatment was constructed by their corresponding relationships in the databases. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore molecular mechanisms associated with MH treatment. The study indicated that rats in the model group showed loss of weight and deteriorated behavior in behavior tests compared with rats in the normal group. A total of 826 lncRNAs, 121 miRNAs, and 954 mRNAs were differentially expressed in the hippocampus of UCMS rats after MH treatment. In addition, 13 miRNAs were selected, and 12 of them were validated in the hippocampus by qRT-PCR. Then, we predicted upstream lncRNAs and downstream mRNAs of the validated miRNAs and interacted with the results of microarrays. Eventually, a lncRNA-miRNA-mRNA regulatory network, responding to MH treatment, was constructed based on the 314 lncRNAs, 11 miRNAs, and 221 mRNAs. KEGG pathways suggested that these genes may be highly related to Wnt signaling, axon guidance, and MAPK signaling pathways. All these results suggest that MH may be a potential representative compound for the treatment of depression, and its mechanism of action is related to the ceRNA modification.
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Affiliation(s)
- Kechao Nie
- Department of Integrated Traditional Chinese & Western Internal Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410001, Hunan, China
| | - Lin Liu
- The First Hospital of Hunan University of Chinese Medicine, Changsha, 410021, Hunan, China
| | - Luqi Peng
- Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Mei Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Chunhu Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Bo Xiao
- Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Zian Xia
- Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Wei Huang
- Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
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Wang Y, Wei J, Chen T, Yang X, Zhao L, Wang M, Dou Y, Du Y, Ni R, Li T, Ma X. A Whole Transcriptome Analysis in Peripheral Blood Suggests That Energy Metabolism and Inflammation Are Involved in Major Depressive Disorder. Front Psychiatry 2022; 13:907034. [PMID: 35633815 PMCID: PMC9136012 DOI: 10.3389/fpsyt.2022.907034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 04/27/2022] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION Previous studies on transcriptional profiles suggested dysregulation of multiple RNA species in major depressive disorder (MDD). However, the interaction between different types of RNA was neglected. Therefore, integration of different RNA species in transcriptome analysis would be helpful for interpreting the functional readout of the transcriptome in MDD. METHODS A whole transcriptome sequencing were performed on the peripheral blood of 15 patients with MDD and 15 matched healthy controls (HCs). The differential expression of miRNAs, lncRNAs, circRNAs, and mRNAs was examined between MDD and HCs using empirical analysis of digital gene expression data in R (edgeR). Weighted correlation network analysis (WGCNA) was used to identify RNA co-expression modules associated with MDD. A ceRNA network was constructed for interpretation of interactions between different RNA species. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to explore potential biological mechanisms associated with MDD. RESULTS Multiple RNAs and co-expression modules were identified to be significantly dysregulated in MDD compared to HCs. Based on the differential RNAs, a ceRNA network that were dysregulated in MDD were constructed. The pathway networks that related to oxidative phosphorylation and the chemokine signaling were found to be associated with MDD. CONCLUSION Our results suggested that the processes of energy metabolism and inflammation may be involved in the pathophysiology of MDD.
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Affiliation(s)
- Yu Wang
- Psychiatric Laboratory and Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.,West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Jinxue Wei
- Psychiatric Laboratory and Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.,West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, China.,Sichuan Clinical Medical Research Center for Mental Disorders, Chengdu, China
| | - Ting Chen
- Psychiatric Laboratory and Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.,West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Xiao Yang
- Psychiatric Laboratory and Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.,West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Liansheng Zhao
- Psychiatric Laboratory and Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.,West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, China.,Sichuan Clinical Medical Research Center for Mental Disorders, Chengdu, China
| | - Min Wang
- Psychiatric Laboratory and Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.,West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Yikai Dou
- Psychiatric Laboratory and Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.,West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Yue Du
- Psychiatric Laboratory and Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.,West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Rongjun Ni
- Psychiatric Laboratory and Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.,West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Tao Li
- Psychiatric Laboratory and Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.,West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Xiaohong Ma
- Psychiatric Laboratory and Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.,West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
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Huan Z, Mei Z, Na H, Xinxin M, Yaping W, Ling L, Lei W, Kejin Z, Yanan L. lncRNA MIR155HG Alleviates Depression-Like Behaviors in Mice by Regulating the miR-155/BDNF Axis. Neurochem Res 2021; 46:935-944. [PMID: 33511575 DOI: 10.1007/s11064-021-03234-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 12/27/2020] [Accepted: 01/06/2021] [Indexed: 12/14/2022]
Abstract
Depression is one of most common psychiatric disorders, and the detailed molecular mechanism remains to be fully elucidated. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophic factor that is decreased and closely involved in the development of depression. Noncoding RNAs are central regulators of cellular activities that modulate target genes. However, the roles of long noncoding RNA (lncRNA) MIR155HG and miRNA-155 (miR-155) in the pathophysiology of depression are unclear. In the present study, we aimed to explore the effects of lncRNA MIR155HG and miR-155 on the development of depression and uncover the underlying molecular mechanism. Real-time quantitative polymerase chain reaction was used to examine the expression of MIR155HG and miR-155. Western blotting was applied to measure the expression of BDNF. A luciferase reporter assay was utilized to determine the regulatory relationship between MIR155HG and miR-155. Our current work found that lncRNA MIR155HG and BDNF levels decreased while miR-155 levels increased in the hippocampal region of CUMS (chronic unpredictable mild stress) mice, a well-accepted mouse model of depression. Moreover, MIR155HG rescued while miR-155 exacerbated the depression-like behaviors of CUMS mice. Through bioinformatics analysis and luciferase reporter assays, we found that MIR155HG directly bound to and negatively modulated the expression of miR-155. Moreover, increased miR-155 was found to repress the expression of BDNF, a critical neurotrophic factor that has been reported to alleviate the depression-like behaviors of CUMS mice. Our present study revealed that lncRNA MIR155HG protected CUMS mice by regulating the miR-155/BDNF axis. Our study aimed to understand the pathophysiology of depression and provided potential therapeutic targets to diagnose and treat depression.
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Affiliation(s)
- Zhang Huan
- Department of Psychology and Psychiatry, The Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xian, 710004, China
| | - Zhu Mei
- Department of Psychology and Psychiatry, The Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xian, 710004, China
| | - Huang Na
- Core Research Laboratory, The Second Affiliated Hospital, College of Medicine, Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Ma Xinxin
- Department of Psychology and Psychiatry, The Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xian, 710004, China
| | - Wang Yaping
- Department of Psychology and Psychiatry, The Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xian, 710004, China
| | - Liu Ling
- Department of Psychology and Psychiatry, The Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xian, 710004, China
| | - Wang Lei
- Department of Psychology and Psychiatry, The Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xian, 710004, China
| | - Zhang Kejin
- School of Medicine, Northwest University, Xi'an, 710069, China
| | - Liu Yanan
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xian, 710069, China.
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Zhang CL, Li YJ, Lu S, Zhang T, Xiao R, Luo HR. Fluoxetine ameliorates depressive symptoms by regulating lncRNA expression in the mouse hippocampus. Zool Res 2021; 42:28-42. [PMID: 33420763 PMCID: PMC7840451 DOI: 10.24272/j.issn.2095-8137.2020.294] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity. The overall prevalence of geriatric depression with clinically significant symptoms is currently on the rise. Recent studies have demonstrated that altered expressions of long non-coding RNAs (lncRNAs) in the brain affect neurodevelopment and manifest modulating functions during the depression. However, most lncRNAs have not yet been studied. Herein, we analyzed the transcriptome of dysregulated lncRNAs to reveal their expressions in a mouse model exhibiting depressive-like behaviors, as well as their corresponding response following antidepressant fluoxetine treatment. A chronic unpredictable mild stress (CUMS) mouse model was applied. A six-week fluoxetine intervention in CUMS-induced mice attenuated depressive-like behaviors. In addition, differential expression analysis of lncRNAs was performed following RNA-sequencing. A total of 282 lncRNAs (134 up-regulated and 148 down-regulated) were differentially expressed in CUMS-induced mice relative to non-stressed counterparts ( P<0.05). Moreover, 370 differentially expressed lncRNAs were identified in CUMS-induced mice after fluoxetine intervention. Gene Ontology (GO) analyses showed an association between significantly dysregulated lncRNAs and protein binding, oxygen binding, and transport activity, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these dysregulated lncRNAs might be involved in inflammatory response pathways. Fluoxetine effectively ameliorated the symptoms of depression in CUMS-induced mice by regulating the expression of lncRNAs in the hippocampus. The findings herein provide valuable insights into the potential mechanism underlying depression in elderly people.
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Affiliation(s)
- Chuan-Ling Zhang
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medical Chemistry, Kunming Institute of Botany, the Chinese Academy of Sciences, Kunming, Yunnan 650201, China.,School of Pharmacy, Inner Mongolia Medical University, Huhhot, Inner Mongolia 010110, China.,University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Yi-Jia Li
- Key Laboratory of Molecular Pathology, Inner Mongolia Medical University, Huhhot, Inner Mongolia 010059, China
| | - Shuang Lu
- Key Laboratory of Molecular Pathology, Inner Mongolia Medical University, Huhhot, Inner Mongolia 010059, China
| | - Ting Zhang
- Key Laboratory of Molecular Pathology, Inner Mongolia Medical University, Huhhot, Inner Mongolia 010059, China
| | - Rui Xiao
- Key Laboratory of Molecular Pathology, Inner Mongolia Medical University, Huhhot, Inner Mongolia 010059, China. E-mail:
| | - Huai-Rong Luo
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medical Chemistry, Kunming Institute of Botany, the Chinese Academy of Sciences, Kunming, Yunnan 650201, China.,Key Laboratory for Aging and Regenerative Medicine, Department of Pharmacology, School of Pharmacy, Southwestern Medical University, Luzhou, Sichuan 646000, China. E-mail:
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Gibbons A, Sundram S, Dean B. Changes in Non-Coding RNA in Depression and Bipolar Disorder: Can They Be Used as Diagnostic or Theranostic Biomarkers? Noncoding RNA 2020; 6:E33. [PMID: 32846922 PMCID: PMC7549354 DOI: 10.3390/ncrna6030033] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 08/20/2020] [Accepted: 08/20/2020] [Indexed: 12/14/2022] Open
Abstract
The similarities between the depressive symptoms of Major Depressive Disorders (MDD) and Bipolar Disorders (BD) suggest these disorders have some commonality in their molecular pathophysiologies, which is not apparent from the risk genes shared between MDD and BD. This is significant, given the growing literature suggesting that changes in non-coding RNA may be important in both MDD and BD, because they are causing dysfunctions in the control of biochemical pathways that are affected in both disorders. Therefore, understanding the changes in non-coding RNA in MDD and BD will lead to a better understanding of how and why these disorders develop. Furthermore, as a significant number of individuals suffering with MDD and BD do not respond to medication, identifying non-coding RNA that are altered by the drugs used to treat these disorders offer the potential to identify biomarkers that could predict medication response. Such biomarkers offer the potential to quickly identify patients who are unlikely to respond to traditional medications so clinicians can refocus treatment strategies to ensure more effective outcomes for the patient. This review will focus on the evidence supporting the involvement of non-coding RNA in MDD and BD and their potential use as biomarkers for treatment response.
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Affiliation(s)
- Andrew Gibbons
- The Florey Institute for Neuroscience and Mental Health, Parkville, The University of Melbourne, Melbourne, Victoria 3052, Australia; (S.S.); (B.D.)
- The Department of Psychiatry, Monash University, 27-31 Wright Street, Clayton, Victoria 3168, Australia
| | - Suresh Sundram
- The Florey Institute for Neuroscience and Mental Health, Parkville, The University of Melbourne, Melbourne, Victoria 3052, Australia; (S.S.); (B.D.)
- The Department of Psychiatry, Monash University, 27-31 Wright Street, Clayton, Victoria 3168, Australia
| | - Brian Dean
- The Florey Institute for Neuroscience and Mental Health, Parkville, The University of Melbourne, Melbourne, Victoria 3052, Australia; (S.S.); (B.D.)
- The Centre for Mental Health, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia
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Meng HY, Chen LQ, Chen LH. The inhibition by human MSCs-derived miRNA-124a overexpression exosomes in the proliferation and migration of rheumatoid arthritis-related fibroblast-like synoviocyte cell. BMC Musculoskelet Disord 2020; 21:150. [PMID: 32143603 PMCID: PMC7060528 DOI: 10.1186/s12891-020-3159-y] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 02/24/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Rheumatoid arthritis is a long-term, progressive autoimmune disease. It is characterized by synovial hyperplasia leading to swelling, stiffness, and joint deformity in more than one joint. Fibroblast-like synoviocytes are the major cell types that make up the synovial intima structure, which is one of the decisive factors in the development and course of rheumatoid arthritis. METHODS The potential therapeutic effects of MSCs-derived miRNA-124a overexpression exosomes were evaluated in vitro by the method including MTT assay and cell cycle test for cell proliferation, scratch wound closure and transwell for cell migration, flow cytometry and western for the apoptosis detection. RESULTS Exosomes derived from human MSCs that overexpression miRNA-124a were prepared and characterized. We found that the pretreatment of this exosome was able to inhibit the proliferation and migration of fibroblast-like synoviocyte cell line and promote the apoptosis of this cell during the co-incubation. CONCLUSIONS Exosomes derived from MSCs were proved to be a suitable vector for the delivery of therapeutic miRNA-124a, and such miRNA-124a overexpression exosomes were expected to provide a new medicine and strategy for the treatment of rheumatoid arthritis.
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Affiliation(s)
- Hong-Yan Meng
- Department of Traditional Chinese Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, P.R. China
| | - Li-Qing Chen
- Health Management Center of Shandong Sunshine Union Hospital Co.,Ltd., Shandong, P.R. China
| | - Li-Hui Chen
- Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, P.R. China.
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Chinese Herbal Formulas Miao-Yi-Ai-Tang Inhibits the Proliferation and Migration of Lung Cancer Cells through Targeting β-Catenin/AXIN and Presents Synergistic Effect with Cisplatin Suppressing Lung Cancer. BIOMED RESEARCH INTERNATIONAL 2020; 2020:2761850. [PMID: 32051824 PMCID: PMC6995313 DOI: 10.1155/2020/2761850] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 11/28/2019] [Accepted: 12/03/2019] [Indexed: 02/08/2023]
Abstract
Objective Lung cancer is one of the major causes of cancer deaths worldwide, and the five-year survival still remains low despite the improvement of screening, prevention, and treatment methods. Chinese herbal medicines have been widely used for tumor prevention and treatment. Miao-Yi-Ai-Tang (Miao) is a novel herbal formulation and shows a potential anticancer effect. Materials and Methods. Human Small Cell Lung Cancer Cell was used for study in vitro. After treatments by Miao and Cisplatin (DDP), the invasion, migration, proliferation, and apoptosis of cells were detected by transwell, wound healing, CCK-8, and flow cytometry, respectively. The expression of β-catenin, AXIN, and c-myc was detected by qRT-PCR and immunohistochemistry staining. Western blotting was applied for measuring the protein expression of β-catenin, AXIN, and c-myc was detected by qRT-PCR and immunohistochemistry staining. Western blotting was applied for measuring the protein expression of Results We found that Miao could inhibit invasion, migration, and proliferation and promote apoptosis of human lung cancer cells. Meanwhile, Miao and DDP presented synergy regulating the proliferation and apoptosis of lung cancer cells. The percentage of lung cancer cells in S and G2 stages was increased markedly by Miao. Besides, the expression of c-myc, AXIN, and β-catenin, AXIN, and c-myc was detected by qRT-PCR and immunohistochemistry staining. Western blotting was applied for measuring the protein expression of Conclusions Chinese herbal formulas Miao could suppress lung cancer through targeting the β-catenin/AXIN signaling pathway. Therefore, our findings may provide a novel strategy for the prevention and treatment of lung cancer.β-catenin, AXIN, and c-myc was detected by qRT-PCR and immunohistochemistry staining. Western blotting was applied for measuring the protein expression of
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Mao J, Li T, Fan D, Zhou H, Feng J, Liu L, Zhang C, Wang X. Abnormal expression of rno_circRNA_014900 and rno_circRNA_005442 induced by ketamine in the rat hippocampus. BMC Psychiatry 2020; 20:1. [PMID: 31898506 PMCID: PMC6939336 DOI: 10.1186/s12888-019-2374-2] [Citation(s) in RCA: 126] [Impact Index Per Article: 25.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Accepted: 11/27/2019] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Recent studies have shown that circular RNA (circRNA) is rich in microRNA (miRNA) binding sites. We have previously demonstrated that the antidepressant effect of ketamine is related to the abnormal expression of various miRNAs in the brain. This study determined the expression profile of circRNAs in the hippocampus of rats treated with ketamine. METHODS The aberrantly expressed circRNAs in rat hippocampus after ketamine injection were analyzed by microarray chip, and we further validated these circRNAs by quantitative reverse-transcription PCR (qRT-PCR). The target genes of the different circRNAs were predicted using bioinformatic analyses, and the functions and signal pathways of these target genes were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. RESULTS Microarray analysis showed that five circRNAs were aberrantly expressed in rat hippocampus after ketamine injection (fold change > 2.0, p < 0.05). The results from the qRT-PCR showed that one of the circRNAs was significantly increased (rno_circRNA_014900; fold change = 2.37; p = 0.03), while one was significantly reduced (rno_circRNA_005442; fold change = 0.37; p = 0.01). We discovered a significant enrichment in several GO terms and pathways associated with depression. CONCLUSION Our findings showed the abnormal expression of ketamine-induced hippocampal circRNAs in rats.
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Affiliation(s)
- Jing Mao
- grid.488387.8School of Clinical Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province People’s Republic of China
| | - Tianmei Li
- grid.488387.8School of Clinical Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province People’s Republic of China
| | - Di Fan
- grid.488387.8School of Clinical Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province People’s Republic of China
| | - Hongli Zhou
- grid.488387.8School of Clinical Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province People’s Republic of China
| | - Jianguo Feng
- grid.488387.8Laboratory of Anesthesiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province People’s Republic of China
| | - Li Liu
- grid.488387.8Department of Anesthesiology, the Affiliated Hospital of Southwest Medical University, No.25, Taiping Road, Luzhou, Sichuan Province 646000 People’s Republic of China
| | - Chunxiang Zhang
- 0000000106344187grid.265892.2Department of Biomedical Engineering, School of Medicine, University of Alabama at Birmingham, Birmingham, AL USA
| | - Xiaobin Wang
- Department of Anesthesiology, the Affiliated Hospital of Southwest Medical University, No.25, Taiping Road, Luzhou, Sichuan Province, 646000, People's Republic of China.
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Yoshino Y, Dwivedi Y. Non-Coding RNAs in Psychiatric Disorders and Suicidal Behavior. Front Psychiatry 2020; 11:543893. [PMID: 33101077 PMCID: PMC7522197 DOI: 10.3389/fpsyt.2020.543893] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 08/14/2020] [Indexed: 12/18/2022] Open
Abstract
It is well known that only a small proportion of the human genome code for proteins; the rest belong to the family of RNAs that do not code for protein and are known as non-coding RNAs (ncRNAs). ncRNAs are further divided into two subclasses based on size: 1) long non-coding RNAs (lncRNAs; >200 nucleotides) and 2) small RNAs (<200 nucleotides). Small RNAs contain various family members that include microRNAs (miRNAs), small interfering RNAs (siRNAs), piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), and small nuclear RNAs (snRNAs). The roles of ncRNAs, especially lncRNAs and miRNAs, are well documented in brain development, homeostasis, stress responses, and neural plasticity. It has also been reported that ncRNAs can influence the development of psychiatric disorders including schizophrenia, major depressive disorder, and bipolar disorder. More recently, their roles are being investigated in suicidal behavior. In this article, we have comprehensively reviewed the findings of lncRNA and miRNA expression changes and their functions in various psychiatric disorders including suicidal behavior. We primarily focused on studies that have been done in postmortem human brain. In addition, we have briefly reviewed the role of other small RNAs (e.g. piwiRNA, siRNA, snRNA, and snoRNAs) and their expression changes in psychiatric illnesses.
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Affiliation(s)
- Yuta Yoshino
- Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Yogesh Dwivedi
- Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, United States
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Chen J, Gu X, Zhou L, Wang S, Zhu L, Huang Y, Cao F. Long non-coding RNA-HOTAIR promotes the progression of sepsis by acting as a sponge of miR-211 to induce IL-6R expression. Exp Ther Med 2019; 18:3959-3967. [PMID: 31656541 PMCID: PMC6812472 DOI: 10.3892/etm.2019.8063] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 06/29/2019] [Indexed: 12/18/2022] Open
Abstract
Sepsis remains the primary cause of death in intensive care units and multiple long non-coding RNAs (lncRNAs) have been demonstrated to be dysregulated in samples of patients with sepsis. However, whether lncRNA-HOTAIR is involved in the etiology of sepsis remains unclear. The aim of the present study was to investigate the role of HOTAIR in sepsis and to reveal the associated mechanisms. A bioinformatics analysis and dual-luciferase reporter assay was performed to evaluate the interaction between HOTAIR and miR-211, as well as miR-211 and IL-6R. An animal model of sepsis was established in mice via cecal ligation and puncture. Interferon (IFN)-γ, interleukin (IL)-6, IL-17, tumor necrosis factor (TNF)-α, IL-1β, IL-6 receptor (R), microRNA (miR)-211 and HOTAIR expression was measured using reverse transcription-quantitative PCR. Cellular proliferation and apoptosis of monocytes were assessed using cell counting kit-8 assay and flow cytometry, respectively. miR-211 was revealed to be targeted by HOTAIR and IL-6R. The expression of IFN-γ, IL-6, IL-17, TNF-α, IL-1β, IL-6R and HOTAIR was significantly upregulated in the septic mice, whereas miR-211 expression was downregulated. The overexpression of hox transcript antisense RNA (HOTAIR) and knockdown of miR-211 were associated with an increased expression of IFN-γ, IL-6, IL-17, TNF-α, IL-1β and IL-6R in monocytes, while the overexpression of miR-211 exhibited the opposite effect. HOTAIR overexpression and miR-211 knockdown significantly inhibited cellular proliferation and promoted monocyte apoptosis, whereas the overexpression of miR-211 exhibited the opposite effects in monocytes. Therefore, HOTAIR may promote the progression of sepsis by indirectly regulating the expression of IL-6R via miR-211.
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Affiliation(s)
- Jianan Chen
- Department of Emergency Intensive Care Unit, Ningbo 6th Hospital, Ningbo, Zhejiang 315040, P.R. China
| | - Xingsheng Gu
- Department of Emergency, Ningbo 6th Hospital, Ningbo, Zhejiang 315040, P.R. China
| | - Li Zhou
- Department of Emergency Intensive Care Unit, Ningbo 6th Hospital, Ningbo, Zhejiang 315040, P.R. China
| | - Shuguang Wang
- Department of Emergency Intensive Care Unit, Ningbo 6th Hospital, Ningbo, Zhejiang 315040, P.R. China
| | - Limei Zhu
- Department of Trauma Orthopedics, Ningbo 6th Hospital, Ningbo, Zhejiang 315040, P.R. China
| | - Yangneng Huang
- Department of Emergency, Ningbo 6th Hospital, Ningbo, Zhejiang 315040, P.R. China
| | - Feng Cao
- Department of Emergency, Ningbo 6th Hospital, Ningbo, Zhejiang 315040, P.R. China
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