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Fettahoğlu İ, Akşahin İC, Yeşiloğlu B, Çelik HEA, Kaymakçı EÇ, Kendirlioğlu BK, Frye M, Özerdem A, Ceylan D. Downregulated mitochondria-encoded long non-coding RNAs in mood disorders. J Affect Disord 2025:119653. [PMID: 40516619 DOI: 10.1016/j.jad.2025.119653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Revised: 06/02/2025] [Accepted: 06/07/2025] [Indexed: 06/16/2025]
Abstract
BACKGROUND Mitochondrial genome-encoded long non-coding RNAs (mt-LncRNAs) that play roles in regulation of energy metabolism and mitochondrial function, both crucial in mood disorder pathogenesis, yet remain poorly explored despite growing interest. This study examines their expression levels in individuals with major depressive disorder (MDD), bipolar disorder (BD), siblings of individuals with BD (SIB), and healthy controls (HC). METHODS Blood samples from 153 participants (31 MDD, 40 BD, 39 SIB, 43 HC) were analyzed for 10 mt-LncRNAs via RT-qPCR. Samples from a subgroup of 15 remitted MDD (MDDREM) patients following 8-week treatment were included for exploratory analysis. A composite score for all LncRNAs, global factor, was derived using principal component analysis. All comparisons were adjusted for age, sex, smoking, BMI, and multiple comparisons. RESULTS Global scores showed overall downregulation in MDD, BD, and SIB compared to HCs, with BD exhibiting the lowest levels (p < 0.01). All mt-LncRNAs were downregulated in BD and SIB, while 8 (excluding ASncmtRNA-2 and 7S RNA) were downregulated in MDD (p < 0.05). Mt-LncRNA levels were lower in BD than in SIB and MDD (p < 0.05), with 6 also lower in SIB compared to MDD (p < 0.05). Exploratory analysis revealed a significant increase in 8 mt-LncRNAs (excluding LIPCAR and 7S RNA) in MDDREM compared to baseline MDD (p < 0.05). CONCLUSION Findings show a significant mt-LncRNA downregulation in mood disorders and suggest genetic transmission as well as a capacity to change with treatment. Further research is needed to explore the genetics and modifiability of mt-LncRNAs in mood disorders.
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Affiliation(s)
- İbrahim Fettahoğlu
- Koç University Research Center for Translational Medicine, İstanbul, Türkiye
| | - İzel Cemre Akşahin
- Koç University Research Center for Translational Medicine, İstanbul, Türkiye; Department of Neuroscience, Graduate School of Health, Koç University, İstanbul, Türkiye
| | - Buket Yeşiloğlu
- Koç University Research Center for Translational Medicine, İstanbul, Türkiye; Department of Neuroscience, Graduate School of Health, Koç University, İstanbul, Türkiye
| | | | | | | | - Mark Frye
- Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, USA
| | - Ayşegül Özerdem
- Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, USA
| | - Deniz Ceylan
- Koç University Research Center for Translational Medicine, İstanbul, Türkiye; Department of Neuroscience, Graduate School of Health, Koç University, İstanbul, Türkiye; Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, USA; Department of Psychiatry, School of Medicine, Koç University, İstanbul, Türkiye.
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Zou B, Zhang Q, Gan H, Qin Y, Zhou Y, Zhai X, Liang P. Long Noncoding RNA GAS5-Involved Progression of Neonatal Hydrocephalus and Inflammatory Responses. Mol Biotechnol 2025; 67:661-672. [PMID: 38429624 DOI: 10.1007/s12033-024-01077-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Accepted: 01/15/2024] [Indexed: 03/03/2024]
Abstract
Intraventricular hemorrhage results in posthemorrhagic hydrocephalus (PHH). Neonatal hydrocephalus remains a challenging disease due to the high failure rate of all management strategies. We evaluated long noncoding RNA growth arrest-specific 5 (GAS5)-mediated network in neonatal hydrocephalus, providing a new direction for the treatment of hydrocephalus. The PHH model was constructed in neonatal rats after intracerebroventricular injection with GAS5, miR-325-3p, and chaperonin containing T-complex protein 1, subunit 8 (CCT8) plasmids, or oligonucleotides. Next, behavioral tests, measurement of serum inflammation, observation of brain tissue pathology, and calculation of hemoglobin and brain water contents were implemented. GAS5, miR-325-3p, and CCT8 expression, in combination with their interactions, was checked. As the results reported, collagenase infusion induced hydrocephalus, impairing neurological function, enhancing inflammation and neuronal apoptosis, and increasing hemoglobin and brain water contents. GAS5 and CCT8 were up-regulated, while miR-325-3p was down-regulated in hydrocephalic rats. Downregulating GAS5/CCT8 or upregulating miR-325-3p could inhibit inflammatory response and improve neurological function in young hydrocephalic rats. GAS5 promotes CCT8 expression through sponge adsorption of miR-325-3p. GAS5 silencing-mediated protections against hydrocephalus were counteracted by CCT8 overexpression. In summary, GAS5 aggravates neonatal hydrocephalus and inflammatory responses in a way of leasing miR-325-3p-involved regulation of CCT8.
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Affiliation(s)
- Bin Zou
- Department of Neurosurgery, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, No. 20, Jinyu Avenue, Yubei District, Chongqing City, 401122, China
| | - Qin Zhang
- Department of Cardiology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing City, 401122, China
| | - Hui Gan
- Chongqing Medical University, Chongqing City, 400016, China
| | - Yue Qin
- Chongqing Medical University, Chongqing City, 400016, China
| | - Yudong Zhou
- Department of Neurosurgery, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, No. 20, Jinyu Avenue, Yubei District, Chongqing City, 401122, China
| | - Xuan Zhai
- Department of Neurosurgery, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, No. 20, Jinyu Avenue, Yubei District, Chongqing City, 401122, China
| | - Ping Liang
- Department of Neurosurgery, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, No. 20, Jinyu Avenue, Yubei District, Chongqing City, 401122, China.
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Zhang Y, Jiang ZY, Wang M, Zhang XT, Ge P, Wang W, Zhang YX, Tong JC. Helicid Alleviates Neuronal Apoptosis of Rats with Depression-Like Behaviors by Downregulating lncRNA-NONRATT030918.2. Mol Neurobiol 2024; 61:10339-10354. [PMID: 38724867 DOI: 10.1007/s12035-024-04192-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 04/18/2024] [Indexed: 11/24/2024]
Abstract
Helicid (HEL) has been found to possess antidepressant pharmacological activity. The paper was to testify to the precise molecular mechanism through which HEL regulates lncRNA-NONRATT030918.2 to exert an antidepressant impression in depression models. A depression model stimulated using chronic unpredictable mild stress (CUMS) was created in rats, and the depressive state of the rats was assessed through behavioral experiments. Additionally, an in vitro model of PC12 cells induced by corticosterone (CORT) was established, and cytoactive was tested using the CCK8. The subcellular localization of the NONRATT030918.2 molecule was confirmed through a fluorescence in situ hybridization experiment. The relationship between NONRATT030918.2, miRNA-128-3p, and Prim1 was analyzed using dual-luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation assay, and RNA pull-down assay. The levels of NONRATT030918.2, miRNA-128-3p, and Prim1 were tested using Q-PCR. Furthermore, the levels of Prim1, Bax, Bcl-2, and caspase3 were checked through Western blot. The HEL can alleviate the depression-like behavior of CUMS rats (P < 0.05), and reduce the mortality of hippocampal via downregulating the level of NONRATT030918.2 (P < 0.05). In CORT-induced PC12 cells, intervention with HEL led to decreased expression of NONRATT030918.2 and Prim1 (P < 0.05), as well as increased expression of miRNA-128-3p (P < 0.05). This suggests that HEL regulates the expression of NONRATT030918.2 to upregulate miRNA-128-3p (P < 0.05), which in turn inhibits CORT-induced apoptosis in PC12 cells by targeting Prim1 (P < 0.05). The NONRATT030918.2/miRNA-128-3p/Prim1 axis could potentially serve as a crucial regulatory network for HEL to exert its neuroprotective effects.
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Affiliation(s)
- Yuan Zhang
- The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, 241001, Anhui, China
- Wannan Medical College, Wuhu, 241002, Anhui, China
- The Second People's Hospital of Lu'an City, Lu'an, 237008, Anhui, China
| | - Zhen-Yi Jiang
- The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, 241001, Anhui, China
- Wannan Medical College, Wuhu, 241002, Anhui, China
| | - Mei Wang
- The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, 241001, Anhui, China
- Wannan Medical College, Wuhu, 241002, Anhui, China
| | - Xiao-Tong Zhang
- The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, 241001, Anhui, China
| | - Peng Ge
- The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, 241001, Anhui, China
- Wannan Medical College, Wuhu, 241002, Anhui, China
| | - Wei Wang
- Wannan Medical College, Wuhu, 241002, Anhui, China
| | | | - Jiu-Cui Tong
- The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, 241001, Anhui, China.
- Wannan Medical College, Wuhu, 241002, Anhui, China.
- Anhui Provincial Engineering Laboratory for Screening and Re-Evaluation of Active Compounds of Herbal Medicines, Southern Anhui, Wuhu, 241002, Anhui, China.
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Zhu L, Guo M, Li K, Guo C, He K. The Association and Prognostic Implications of Long Non-Coding RNAs in Major Psychiatric Disorders, Alzheimer's Diseases and Parkinson's Diseases: A Systematic Review. Int J Mol Sci 2024; 25:10995. [PMID: 39456775 PMCID: PMC11507000 DOI: 10.3390/ijms252010995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/09/2024] [Accepted: 10/11/2024] [Indexed: 10/28/2024] Open
Abstract
The prevalence of psychiatric disorders and neurodegenerative diseases is steadily increasing, placing a significant burden on both society and individuals. Given the intricate and multifaceted nature of these diseases, the precise underlying mechanisms remain elusive. Consequently, there is an increasing imperative to investigate the mechanisms, identify specific target sites for effective treatment, and provide for accurate diagnosis of patients with these diseases. Numerous studies have revealed significant alterations in the expression of long non-coding RNAs (lncRNAs) in psychiatric disorders and neurodegenerative diseases, suggesting their potential to increase the probability of these diseases. Moreover, these findings propose that lncRNAs could be used as highly valuable biomarkers in diagnosing and treating these diseases, thereby offering novel insights for future clinical interventions. The review presents a comprehensive summary of the origin, biological functions, and action mechanisms of lncRNAs, while exploring their implications in the pathogenesis of psychiatric disorders and neurodegenerative diseases and their potential utility as biomarkers.
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Affiliation(s)
- Lin Zhu
- College of Life Sciences and Food Engineering, Inner Mongolia Minzu University, Tongliao 028000, China; (L.Z.); (K.L.); (C.G.)
| | - Meng Guo
- Finance Office, Inner Mongolia Minzu University, Tongliao 028000, China;
| | - Ke Li
- College of Life Sciences and Food Engineering, Inner Mongolia Minzu University, Tongliao 028000, China; (L.Z.); (K.L.); (C.G.)
| | - Chuang Guo
- College of Life Sciences and Food Engineering, Inner Mongolia Minzu University, Tongliao 028000, China; (L.Z.); (K.L.); (C.G.)
| | - Kuanjun He
- College of Life Sciences and Food Engineering, Inner Mongolia Minzu University, Tongliao 028000, China; (L.Z.); (K.L.); (C.G.)
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Inserra A, Campanale A, Rezai T, Romualdi P, Rubino T. Epigenetic mechanisms of rapid-acting antidepressants. Transl Psychiatry 2024; 14:359. [PMID: 39231927 PMCID: PMC11375021 DOI: 10.1038/s41398-024-03055-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 08/19/2024] [Accepted: 08/21/2024] [Indexed: 09/06/2024] Open
Abstract
BACKGROUND Rapid-acting antidepressants (RAADs), including dissociative anesthetics, psychedelics, and empathogens, elicit rapid and sustained therapeutic improvements in psychiatric disorders by purportedly modulating neuroplasticity, neurotransmission, and immunity. These outcomes may be mediated by, or result in, an acute and/or sustained entrainment of epigenetic processes, which remodel chromatin structure and alter DNA accessibility to regulate gene expression. METHODS In this perspective, we present an overview of the known mechanisms, knowledge gaps, and future directions surrounding the epigenetic effects of RAADs, with a focus on the regulation of stress-responsive DNA and brain regions, and on the comparison with conventional antidepressants. MAIN BODY Preliminary correlative evidence indicates that administration of RAADs is accompanied by epigenetic effects which are similar to those elicited by conventional antidepressants. These include changes in DNA methylation, post-translational modifications of histones, and differential regulation of non-coding RNAs in stress-responsive chromatin areas involved in neurotrophism, neurotransmission, and immunomodulation, in stress-responsive brain regions. Whether these epigenetic changes causally contribute to the therapeutic effects of RAADs, are a consequence thereof, or are unrelated, remains unknown. Moreover, the potential cell type-specificity and mechanisms involved are yet to be fully elucidated. Candidate mechanisms include neuronal activity- and serotonin and Tropomyosine Receptor Kinase B (TRKB) signaling-mediated epigenetic changes, and direct interaction with DNA, histones, or chromatin remodeling complexes. CONCLUSION Correlative evidence suggests that epigenetic changes induced by RAADs accompany therapeutic and side effects, although causation, mechanisms, and cell type-specificity remain largely unknown. Addressing these research gaps may lead to the development of novel neuroepigenetics-based precision therapeutics.
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Affiliation(s)
- Antonio Inserra
- Department of Psychiatry, McGill University, Montreal, QC, Canada.
- Behavioral Neuroscience Laboratory, University of South Santa Catarina (UNISUL), Tubarão, Brazil., Tubarão, Brazil.
| | | | - Tamim Rezai
- Department of Psychiatry, McGill University, Montreal, QC, Canada
| | - Patrizia Romualdi
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Tiziana Rubino
- Department of Biotechnology and Life Sciences and Neuroscience Center, University of Insubria, Varese, Italy
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Huang Y, Jin Y, Yao S, Nan G, Mao Y. LncRNA NEAT1 Inhibits Neuronal Apoptosis and Induces Neuronal Viability of Depressed Rats Via microRNA-320-3p/CRHR1 Axis. Neurochem Res 2024; 49:2352-2363. [PMID: 35075548 DOI: 10.1007/s11064-021-03508-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 12/06/2021] [Accepted: 12/08/2021] [Indexed: 10/19/2022]
Abstract
Long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to be involved in depression. This study aims to investigate the mechanism of NEAT1/microRNA (miR)-320-3p/Corticotropin-releasing hormone receptor 1 (CRHR1) axis in depressed rats. Rats with depression-like behaviors were prepared by exposing the rats to chronic unpredictable mild stress. Behavioral functions, pathological damage, neuronal apoptosis and monoamine neurotransmitter were examined in depressed rats . Primary hippocampal neurons were injured through simulation with corticosterone(CORT). Cell viability and apoptosis were measured in CORT-Induced hippocampal neurons. The binding relationship between NEAT1 and miR-320-3p and the targeting relationship between miR-320-3p and CRHR1 were detected. Elevated NEAT1, CRHR1 and reduced miR-320-3p exhibited in depressed rats and CORT-treated hippocampal neurons, NEAT1 bound to miR-320-3p to target CRHR1. Silencing NEAT1 or elevating miR-320-3p improved behavioral functions, attenuated pathological damage and apoptosis in the hippocampus, and increased monoamine neurotransmitter in depressed rats. Repression of NEAT1 or promotion of miR-320-3p enhanced viability and suppressed apoptosis of CORT-treated hippocampal neurons. The study highlights that NEAT1 competitively binds to miR-320-3p to up-regulate CRHR1 expression, thereby promoting hippocampal damage of depressed rats.
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Affiliation(s)
- Yujing Huang
- Department of Neurology, Associate Chief Physicia, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China
| | - Yinshi Jin
- Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China
| | - Shuai Yao
- Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China
| | - Guangxian Nan
- Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China
| | - Ying Mao
- Department of Neurology, China-Japan Union Hospital of Jilin University, Attending doctorNo. 126 Xiantai Street, Changchun, 130033, Jilin, China.
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Rasaei N, Esmaeili F, Khadem A, Yekaninejad MS, Mirzaei K. lncRNA TUG1 transcript levels and psychological disorders: insights into interplay of glycemic index and glycemic load. BMC Med Genomics 2024; 17:221. [PMID: 39198825 PMCID: PMC11351548 DOI: 10.1186/s12920-024-01976-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Accepted: 07/31/2024] [Indexed: 09/01/2024] Open
Abstract
BACKGROUND There is an association between obesity and psychological disorders such as depression, anxiety, and stress. Environmental factors and genetics play a crucial role in this regard. Several long non-coding RNAs (lncRNAs) are involved in the pathophysiology of the nervous system. Additionally, we intend to investigate how dietary glycemic index and load relate to psychological disorders in women with obesity and overweight by identifying the possible interaction with metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and taurine upregulated gene 1 (TUG1). METHODS 267 overweight or obese women between the ages of 18 and 48 were recruited for the current study. A reliable and validated food frequency questionnaire (FFQ) consisting of 147 items assessed food consumption, glycemic load (GL), and glycemic index (GI). Depression-Anxiety-Stress Scales (DASS-21) were used to assess mental well-being. A real-time polymerase chain reaction (PCR) was used to assess transcript levels for lncRNAs MALAT1 and TUG1. RESULTS In obese and overweight women, a positive correlation was found between anxiety and MALAT1 mRNA levels (P = 0.007, CC = 0.178). Age, energy intake, physical activity, total fat, income, marriage, thyroid, and BMI were adjusted, and GI and TUG1 were positively correlated on DASS-21 (β = 0.006, CI = 0.001, 0.01, P = 0.031), depression (β = 0.002, CI = 0.001, 0.004, P = 0.019), Stress (β = 0.003, CI = 0.001, 0.005, P = 0.027). The interaction of GL and TUG1 on stress was also observed (β = 0.03, CI = 0.001, 0.07, P = 0.048). CONCLUSIONS The lncRNA TUG1 appears to be associated with depression and stress through interaction with GI and correlated with stress by interaction with GL. To establish this concept, further research is required.
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Affiliation(s)
- Niloufar Rasaei
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), P.O. Box:14155-6117, Tehran, Iran
- Network of Interdisciplinarity in Neonates and Infants (NINI), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Fataneh Esmaeili
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Khadem
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Mir Saeed Yekaninejad
- Department of Epidemiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Khadijeh Mirzaei
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), P.O. Box:14155-6117, Tehran, Iran.
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Sane S, Ebrahimi V, Shirvani Farsani Z, Ghafouri-Fard S. Assessment of Expression of lncRNAs in Autistic Patients. J Mol Neurosci 2024; 74:81. [PMID: 39186094 DOI: 10.1007/s12031-024-02258-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 08/17/2024] [Indexed: 08/27/2024]
Abstract
Autism is a severe neurodevelopmental condition with unknown pathobiology. Nevertheless, multiple pieces of evidence suggest long non-coding RNA (lncRNA) dysregulation may be a contributing factor to this disorder. We investigated the association between the expression of five specific lncRNAs and autism. Peripheral blood was collected from 30 children with autism and 41 healthy children. The expression levels of PCAT-29, lincRNA-ROR, LINC-PINT, lincRNA-p21, and PCAT-1 were calculated. Then, their significance as biomarkers was also evaluated. The expression of LincRNA-ROR (27 times), LINC-PINT (5.26 times), LincRNA-p21 (4.54 times), PCAT-29 (16.66 times), and PCAT-1 (25 times) genes was significantly decreased in patients compared to the control group (p values < 0.05). According to the ROC curve analysis for each lncRNA, LincRNA-ROR, LINC-PINT, LincRNA-p21, PCAT-29, and PCAT-1 lncRNAs with diagnostic power of 0.85, 0.67, 0.64, 0.74, and 0.84, respectively, could be used as diagnostic biomarkers for autism. Additionally, significant positive correlations were reported between expression levels of PCAT-1 and PCAT-29 genes. Moreover, a positive correlation was detected between expression levels of lincRNA-ROR and patients' age. The current study shows further pieces of evidence for deregulation of lncRNAs in autistic patients that show these lncRNAs may play an important part in the pathogenesis of ASD. However, the role of lncRNA in the neurobiology of autism needs to be investigated further.
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Affiliation(s)
- Saba Sane
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Vera Ebrahimi
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Zeinab Shirvani Farsani
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Dini N, Taheri M, Shirvani-Farsani Z. The expression analysis of long noncoding RNAs PCAT-1, PCAT-29, and MER11C in bipolar disorder. BMC Psychiatry 2024; 24:524. [PMID: 39044190 PMCID: PMC11264442 DOI: 10.1186/s12888-024-05974-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 07/17/2024] [Indexed: 07/25/2024] Open
Abstract
Long non-coding RNAs (lncRNAs) are transcripts with a length of usually more than 200 nucleotides (nt) that have promised functions in varied biological processes. lncRNAs participate in the regulation of differentiation, development, and function of the brain. Thus, their dysregulation might play important roles in the etiology of neurological disorders such as BD. In this study, the expression level of PCAT-1, PCAT-29, and MER11C lncRNAs was evaluated in the blood of BD patients compared to the control group. Peripheral blood mononuclear cells of 50 BD type I patients and 50 healthy individuals were isolated. The RNAs were extracted and cDNA was synthesized. Then, the expression level of the desired lncRNAs was measured through Real-Time PCR. The expression levels of PCAT-29 and MER11C lncRNAs were significantly lower in BD patients compared to controls. However, the expression level of PCAT-1 was not significantly different between these two sets of samples. According to the ROC curve, PCAT-29 and MER11C had significant diagnostic power for the differentiation of BD patients from controls. Taken together, our results indicate dysregulation of two lncRNAs in patients with BD and the possible roles of these lncRNAs in the neuropathology of bipolar disorder.
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Affiliation(s)
- Niloofar Dini
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Mohammad Taheri
- Institute of Human Genetics, Jena University Hospital, Jena, Germany.
| | - Zeinab Shirvani-Farsani
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
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Shi L, Han X, Liu F, Long J, Jin Y, Chen S, Duan G, Yang H. Review on Long Non-Coding RNAs as Biomarkers and Potentially Therapeutic Targets for Bacterial Infections. Curr Issues Mol Biol 2024; 46:7558-7576. [PMID: 39057090 PMCID: PMC11276060 DOI: 10.3390/cimb46070449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 07/13/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
The confrontation between humans and bacteria is ongoing, with strategies for combating bacterial infections continually evolving. With the advancement of RNA sequencing technology, non-coding RNAs (ncRNAs) associated with bacterial infections have garnered significant attention. Recently, long ncRNAs (lncRNAs) have been identified as regulators of sterile inflammatory responses and cellular defense against live bacterial pathogens. They are involved in regulating host antimicrobial immunity in both the nucleus and cytoplasm. Increasing evidence indicates that lncRNAs are critical for the intricate interactions between host and pathogen during bacterial infections. This paper emphatically elaborates on the potential applications of lncRNAs in clinical hallmarks, cellular damage, immunity, virulence, and drug resistance in bacterial infections in greater detail. Additionally, we discuss the challenges and limitations of studying lncRNAs in the context of bacterial infections and highlight clear directions for this promising field.
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Affiliation(s)
| | | | | | | | | | | | | | - Haiyan Yang
- Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou 450001, China; (L.S.); (X.H.); (F.L.); (J.L.); (Y.J.); (S.C.); (G.D.)
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Xie Y, Chen L, Wang L, Liu T, Zheng Y, Si L, Ge H, Xu H, Xiao L, Wang G. Single-nucleus transcriptomic analysis reveals the relationship between gene expression in oligodendrocyte lineage and major depressive disorder. J Transl Med 2024; 22:109. [PMID: 38281050 PMCID: PMC10822185 DOI: 10.1186/s12967-023-04727-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Accepted: 11/13/2023] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Major depressive disorder (MDD) is a common mental illness that affects millions of people worldwide and imposes a heavy burden on individuals, families and society. Previous studies on MDD predominantly focused on neurons and employed bulk homogenates of brain tissues. This paper aims to decipher the relationship between oligodendrocyte lineage (OL) development and MDD at the single-cell resolution level. METHODS Here, we present the use of a guided regularized random forest (GRRF) algorithm to explore single-nucleus RNA sequencing profiles (GSE144136) of the OL at four developmental stages, which contains dorsolateral prefrontal cortex of 17 healthy controls (HC) and 17 MDD cases, generated by Nagy C et al. We prioritized and ordered differentially expressed genes (DEGs) based on Nagy et al., which could predominantly discriminate cells in the four developmental stages and two adjacent developmental stages of the OL. We further screened top-ranked genes that distinguished between HC and MDD in four developmental stages. Moreover, we estimated the performance of the GRRF model via the area under the curve value. Additionally, we validated the pivotal candidate gene Malat1 in animal models. RESULTS We found that, among the four developmental stages, the onset development of OL (OPC2) possesses the best predictive power for distinguishing HC and MDD, and long noncoding RNA MALAT1 has top-ranked importance value in candidate genes of four developmental stages. In addition, results of fluorescence in situ hybridization assay showed that Malat1 plays a critical role in the occurrence of depression. CONCLUSIONS Our work elucidates the mechanism of MDD from the perspective of OL development at the single-cell resolution level and provides novel insight into the occurrence of depression.
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Affiliation(s)
- Yinping Xie
- Institute of Neuropsychiatry, Renmin Hospital of Wuhan University, Wuhan, China
| | - Lijuan Chen
- Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China
| | - Leimin Wang
- School of Automation, China University of Geosciences, Wuhan, China
| | - Tongou Liu
- The First Clinical College of Hubei University of Chinese Medicine, Wuhan, China
| | - Yage Zheng
- Judicial Appraisal Institute, Renmin Hospital of Hubei Province, Wuhan, China
| | - Lujia Si
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China
| | - Hailong Ge
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China
| | - Hong Xu
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ling Xiao
- Institute of Neuropsychiatry, Renmin Hospital of Wuhan University, Wuhan, China.
| | - Gaohua Wang
- Institute of Neuropsychiatry, Renmin Hospital of Wuhan University, Wuhan, China.
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12
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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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13
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Ceylan D, Karacicek B, Tufekci KU, Aksahin IC, Senol SH, Genc S. Mitochondrial DNA oxidation, methylation, and copy number alterations in major and bipolar depression. Front Psychiatry 2023; 14:1304660. [PMID: 38161720 PMCID: PMC10755902 DOI: 10.3389/fpsyt.2023.1304660] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 11/20/2023] [Indexed: 01/03/2024] Open
Abstract
Background Mood disorders are common disabling psychiatric disorders caused by both genetic and environmental factors. Mitochondrial DNA (mtDNA) modifications and epigenetics are promising areas of research in depression since mitochondrial dysfunction has been associated with depression. In this study we aimed to investigate the mtDNA changes in depressive disorder (MDD) and bipolar disorder (BD). Methods Displacement loop methylation (D-loop-met), relative mtDNA copy number (mtDNA-cn) and mtDNA oxidation (mtDNA-oxi) were investigated in DNA samples of individuals with MDD (n = 34), BD (n = 23), and healthy controls (HC; n = 40) using the Real-Time Polymerase Chain Reaction (RT-PCR). Blood samples were obtained from a subset of individuals with MDD (n = 15) during a depressive episode (baseline) and after remission (8th week). Results The study groups exhibited significant differences in D-loop-met (p = 0.020), while relative mtDNA-cn and mtDNA-oxi showed comparable results. During the remission phase (8th week), there were lower levels of relative mtDNA-cn (Z = -2.783, p = 0.005) and D-loop-met (Z = -3.180, p = 0.001) compared to the acute MDD baseline, with no significant change in mtDNA-oxi levels (Z = -1.193, p = 0.233). Conclusion Our findings indicate significantly increased D-loop methylation in MDD compared to BD and HCs, suggesting distinct mtDNA modifications in these conditions. Moreover, the observed alterations in relative mtDNA-cn and D-loop-met during remission suggest a potential role of mtDNA alterations in the pathophysiology of MDD. Future studies may provide valuable insights into the dynamics of mtDNA modifications in both disorders and their response to treatment.
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Affiliation(s)
- Deniz Ceylan
- Affective Laboratory, Koç University Research Center for Translational Medicine, Istanbul, Türkiye
- Department of Psychiatry, Koç University Hospital, Istanbul, Türkiye
| | - Bilge Karacicek
- Izmir Biomedicine and Genome Center, Genç Lab, Izmir, Türkiye
| | - Kemal Ugur Tufekci
- Brain and Neuroscience Research and Application Center, Izmir Demokrasi University, Izmir, Türkiye
- Vocational School of Health Services, Izmir Democracy University, Izmir, Türkiye
| | - Izel Cemre Aksahin
- Affective Laboratory, Koç University Research Center for Translational Medicine, Istanbul, Türkiye
- Graduate School of Health Sciences, Koç University, Istanbul, Türkiye
| | - Sevin Hun Senol
- Department of Psychiatry, Koç University Hospital, Istanbul, Türkiye
| | - Sermin Genc
- Izmir Biomedicine and Genome Center, Genç Lab, Izmir, Türkiye
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14
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Wang L, Wang J, Yang Z, Wang Y, Zhao T, Luo W, Liang T, Yang Z. Traditional herbs: mechanisms to combat cellular senescence. Aging (Albany NY) 2023; 15:14473-14505. [PMID: 38054830 PMCID: PMC10756111 DOI: 10.18632/aging.205269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 10/15/2023] [Indexed: 12/07/2023]
Abstract
Cellular senescence plays a very important role in the ageing of organisms and age-related diseases that increase with age, a process that involves physiological, structural, biochemical and molecular changes in cells. In recent years, it has been found that the active ingredients of herbs and their natural products can prevent and control cellular senescence by affecting telomerase activity, oxidative stress response, autophagy, mitochondrial disorders, DNA damage, inflammatory response, metabolism, intestinal flora, and other factors. In this paper, we review the research information on the prevention and control of cellular senescence in Chinese herbal medicine through computer searches of PubMed, Web of Science, Science Direct and CNKI databases.
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Affiliation(s)
- Lei Wang
- Graduate School, Guangxi University of Chinese Medicine, Nanning, Guangxi 530222, China
- Department of Medicine, Faculty of Chinese Medicine Science Guangxi University of Chinese Medicine, Nanning, Guangxi 530222, China
| | - Jiahui Wang
- Department of Medicine, Faculty of Chinese Medicine Science Guangxi University of Chinese Medicine, Nanning, Guangxi 530222, China
| | - Zhihui Yang
- Department of Medicine, Faculty of Chinese Medicine Science Guangxi University of Chinese Medicine, Nanning, Guangxi 530222, China
| | - Yue Wang
- Department of Medicine, Faculty of Chinese Medicine Science Guangxi University of Chinese Medicine, Nanning, Guangxi 530222, China
| | - Tiejian Zhao
- Department of Physiology, College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi 530222, China
| | - Weisheng Luo
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi 530000, China
| | - Tianjian Liang
- Department of Medicine, Faculty of Chinese Medicine Science Guangxi University of Chinese Medicine, Nanning, Guangxi 530222, China
| | - Zheng Yang
- Department of Medicine, Faculty of Chinese Medicine Science Guangxi University of Chinese Medicine, Nanning, Guangxi 530222, China
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15
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Yuan M, Yang B, Rothschild G, Mann JJ, Sanford LD, Tang X, Huang C, Wang C, Zhang W. Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential. Signal Transduct Target Ther 2023; 8:309. [PMID: 37644009 PMCID: PMC10465587 DOI: 10.1038/s41392-023-01519-z] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 05/14/2023] [Accepted: 05/31/2023] [Indexed: 08/31/2023] Open
Abstract
Major depressive disorder (MDD) is a chronic, generally episodic and debilitating disease that affects an estimated 300 million people worldwide, but its pathogenesis is poorly understood. The heritability estimate of MDD is 30-40%, suggesting that genetics alone do not account for most of the risk of major depression. Another factor known to associate with MDD involves environmental stressors such as childhood adversity and recent life stress. Recent studies have emerged to show that the biological impact of environmental factors in MDD and other stress-related disorders is mediated by a variety of epigenetic modifications. These epigenetic modification alterations contribute to abnormal neuroendocrine responses, neuroplasticity impairment, neurotransmission and neuroglia dysfunction, which are involved in the pathophysiology of MDD. Furthermore, epigenetic marks have been associated with the diagnosis and treatment of MDD. The evaluation of epigenetic modifications holds promise for further understanding of the heterogeneous etiology and complex phenotypes of MDD, and may identify new therapeutic targets. Here, we review preclinical and clinical epigenetic findings, including DNA methylation, histone modification, noncoding RNA, RNA modification, and chromatin remodeling factor in MDD. In addition, we elaborate on the contribution of these epigenetic mechanisms to the pathological trait variability in depression and discuss how such mechanisms can be exploited for therapeutic purposes.
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Affiliation(s)
- Minlan Yuan
- Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Biao Yang
- Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Gerson Rothschild
- Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA
| | - J John Mann
- Department of Psychiatry, Columbia University, New York, NY, 10032, USA
- Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, 10032, USA
- Department of Radiology, Columbia University, New York, NY, 10032, USA
| | - Larry D Sanford
- Sleep Research Laboratory, Center for Integrative Neuroscience and Inflammatory Diseases, Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA, USA
| | - Xiangdong Tang
- Sleep Medicine Center, Department of Respiratory and Critical Care Medicine, Mental Health Center, Translational Neuroscience Center, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Canhua Huang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Chuang Wang
- Department of Pharmacology, and Provincial Key Laboratory of Pathophysiology in School of Medicine, Ningbo University, Ningbo, Zhejiang, 315211, China.
| | - Wei Zhang
- Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
- Medical Big Data Center, Sichuan University, Chengdu, 610041, China.
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16
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Zhong XL, Du Y, Chen L, Cheng Y. The emerging role of long noncoding RNA in depression and its implications in diagnostics and therapeutic responses. J Psychiatr Res 2023; 164:251-258. [PMID: 37385004 DOI: 10.1016/j.jpsychires.2023.06.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 05/18/2023] [Accepted: 06/15/2023] [Indexed: 07/01/2023]
Abstract
Depression is one of the most common mental illnesses, affecting more than 350 million people worldwide. However, the occurrence of depression is a complex process involving genetic, physiological, psychological, and social factors, and the underlying mechanisms of its pathogenesis remain unclear. With advances in sequencing technology and epigenetic studies, increasing research evidence suggests that long noncoding RNAs (lncRNAs) play nonnegligible roles in the development of depression and may be involved in the pathogenesis of depression through multiple pathways, including regulating neurotrophic factors and other growth factors and affecting synaptic function. In addition, significant alterations in lncRNA expression profiles in peripheral blood and different brain regions of patients and model animals with depression suggest that lncRNAs may function as biomarkers for the differential diagnosis of depression and other psychiatric disorders and may also be potential therapeutic targets. In this paper, the biological functions of lncRNAs are briefly described, and the functional roles and abnormal expression of lncRNAs in the development, diagnosis and treatment of depression are reviewed.
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Affiliation(s)
- Xiao-Lin Zhong
- Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China
| | - Yang Du
- Key Laboratory of Ethnomedicine of Ministry of Education, School of Pharmacy, Minzu University of China, Beijing, China
| | - Lei Chen
- Key Laboratory of Ethnomedicine of Ministry of Education, School of Pharmacy, Minzu University of China, Beijing, China
| | - Yong Cheng
- Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China; Key Laboratory of Ethnomedicine of Ministry of Education, School of Pharmacy, Minzu University of China, Beijing, China; Institute of National Security, Minzu University of China, Beijing, China.
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17
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Zou ZL, Ye Y, Zhou B, Zhang Y. Identification and characterization of noncoding RNAs-associated competing endogenous RNA networks in major depressive disorder. World J Psychiatry 2023; 13:36-49. [PMID: 36925948 PMCID: PMC10011943 DOI: 10.5498/wjp.v13.i2.36] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 12/06/2022] [Accepted: 01/23/2023] [Indexed: 02/17/2023] Open
Abstract
BACKGROUND Major depressive disorder (MDD) is a common and serious mental illness. Many novel genes in MDD have been characterized by high-throughput methods such as microarrays or sequencing. Recently, noncoding RNAs (ncRNAs) were suggested to be involved in the complicated environmental-genetic regulatory network of MDD occurrence; however, the interplay among RNA species, including protein-coding RNAs and ncRNAs, in MDD remains unclear.
AIM To investigate the RNA expression datasets downloaded from a public database and construct a network based on differentially expressed long noncoding RNA (lncRNAs), microRNAs (miRNAs), and mRNAs between MDD and controls.
METHODS Gene expression data were searched in NCBI Gene Expression Omnibus using the search term “major depressive disorder.” Six array datasets from humans were related to the search term: GSE19738, GSE32280, GSE38206, GSE52790, GSE76826, and GSE81152. These datasets were processed for initial assessment and subjected to quality control and differential expression analysis. Differentially expressed lncRNAs, miRNAs, and mRNAs were determined, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed, and protein-protein interaction network was generated. The results were analyzed for their association with MDD.
RESULTS After analysis, 3 miRNAs, 12 lncRNAs, and 33 mRNAs were identified in the competing endogenous RNA network. Two of these miRNAs were earlier shown to be involved in psychiatric disorders, and differentially expressed mRNAs were found to be highly enriched in pathways related to neurogenesis and neuroplasticity as per Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The expression of hub gene fatty acid 2-hydroxylase was enriched, and the encoded protein was found to be involved in myelin formation, indicating that neurological development and signal transduction are involved in MDD pathogenesis.
CONCLUSION The present study presents candidate ncRNAs involved in the neurogenesis and neuroplasticity pathways related to MDD.
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Affiliation(s)
- Zhi-Li Zou
- Department of Psychosomatic, Sichuan Academy of Medical Science & Sichuan Provincial People’s Hospital, Chengdu 610072, Sichuan Province, China
| | - Yu Ye
- Sichuan Provincial Center for Mental Health, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 611130, Sichuan Province, China
| | - Bo Zhou
- Department of Psychosomatic, Sichuan Academy of Medical Science & Sichuan Provincial People’s Hospital, Chengdu 610072, Sichuan Province, China
| | - Yuan Zhang
- Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu 610072, Sichuan Province, China
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18
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Sharifi G, Eghtedarian R, Taheri M, Hussen BM, Eslami S, Ghafouri-Fard S, Sayad A. Assessment of Treg-related lncRNAs in epilepsy. Front Mol Neurosci 2023; 15:1031314. [PMID: 36776769 PMCID: PMC9908604 DOI: 10.3389/fnmol.2022.1031314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 12/14/2022] [Indexed: 01/27/2023] Open
Abstract
Recent studies have shown dysregulation of several groups of long non-coding RNAs in the context of epilepsy. According to evidence regarding the role of regulatory T cells in this disorder, we examined expression levels of regulatory T cell-related lncRNAs, namely TH2-LCR, RMRP, IFNG-AS1 (NEST), MAFTRR and FLICR in the blood of epileptic cases compared with controls. Expression of RMRP was lower in patients with refractory epilepsy compared with controls [expression ratio (95% CI) = 0.32 (0.13-0.8), adjusted p-value = 0.0008]. Besides, its expression was lower in refractory patients vs. non-refractory patients [expression ratio (95% CI) = 0.2 (0.1-0.41), adjusted p-value < 0.0001]. Expression of TH2-LCR was lower in refractory patients vs. controls [expression ratio (95% CI) = 0.4 (0.17-0.93), adjusted p-value = 0.0044] and in refractory patients vs. non-refractory ones [Expression ratio = 0.28 (0.19-0.58), p-value < 0.0001]. Expression of NEST was higher in total patients [expression ratio (95% CI) = 2.48 (1.15-5.27), adjusted p-value = 0.0012] and in both groups of patients compared with controls. However, its expression was not different between refractory and non-refractory cases. Similarly, FLICR and MAFTRR were over-expressed in total cases and both groups of patients compared with controls, but their expressions were similar between refractory and non-refractory cases. MAFTRR could differentiate between total epileptic cases and controls with AUC value of 0.8. This lncRNA could separate refractory and non-refractory cases from healthy controls with AUC values of 0.73 and 0.88, respectively. This study provides evidence for deregulation of regulatory T cell-related lncRNAs in epilepsy and their potential role as diagnostic markers in this condition.
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Affiliation(s)
- Guive Sharifi
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reyhane Eghtedarian
- Phytochemistry Research Center, Shahid Beheshti University of Sciences, Tehran, Iran
| | - Mohammad Taheri
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Institute of Human Genetics, Jena University Hospital, Jena, Germany
| | - Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Iraq,Center of Research and Strategic Studies, Lebanese French University, Erbil, Iraq
| | - Solat Eslami
- Department of Medical Biotechnology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran,Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Soudeh Ghafouri-Fard
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran,*Correspondence: Soudeh Ghafouri-Fard, ✉
| | - Arezou Sayad
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Arezou Sayad, ✉
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Denham AN, Drake J, Gavrilov M, Taylor ZN, Bacanu SA, Vladimirov VI. Long Non-Coding RNAs: The New Frontier into Understanding the Etiology of Alcohol Use Disorder. Noncoding RNA 2022; 8:59. [PMID: 36005827 PMCID: PMC9415279 DOI: 10.3390/ncrna8040059] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 07/29/2022] [Accepted: 08/02/2022] [Indexed: 11/28/2022] Open
Abstract
Alcohol use disorder (AUD) is a complex, chronic, debilitating condition impacting millions worldwide. Genetic, environmental, and epigenetic factors are known to contribute to the development of AUD. Long non-coding RNAs (lncRNAs) are a class of regulatory RNAs, commonly referred to as the "dark matter" of the genome, with little to no protein-coding potential. LncRNAs have been implicated in numerous processes critical for cell survival, suggesting that they play important functional roles in regulating different cell processes. LncRNAs were also shown to display higher tissue specificity than protein-coding genes and have a higher abundance in the brain and central nervous system, demonstrating a possible role in the etiology of psychiatric disorders. Indeed, genetic (e.g., genome-wide association studies (GWAS)), molecular (e.g., expression quantitative trait loci (eQTL)) and epigenetic studies from postmortem brain tissues have identified a growing list of lncRNAs associated with neuropsychiatric and substance use disorders. Given that the expression patterns of lncRNAs have been associated with widespread changes in the transcriptome, including methylation, chromatin architecture, and activation or suppression of translational activity, the regulatory nature of lncRNAs may be ubiquitous and an innate component of gene regulation. In this review, we present a synopsis of the functional impact that lncRNAs may play in the etiology of AUD. We also discuss the classifications of lncRNAs, their known functional roles, and therapeutic advancements in the field of lncRNAs to further clarify the functional relationship between lncRNAs and AUD.
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Affiliation(s)
- Allie N. Denham
- Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX 77807, USA
- Department of Psychiatry, College of Medicine, University of Arizona Phoenix, Phoenix, AZ 85004, USA
| | - John Drake
- Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX 77807, USA
- Department of Psychiatry, College of Medicine, University of Arizona Phoenix, Phoenix, AZ 85004, USA
- MSCI Program, Texas A&M University, Bryan, TX 77807, USA
| | - Matthew Gavrilov
- Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX 77807, USA
| | - Zachary N. Taylor
- Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX 77807, USA
- Department of Psychiatry, College of Medicine, University of Arizona Phoenix, Phoenix, AZ 85004, USA
| | - Silviu-Alin Bacanu
- Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23219, USA
- Departent of Psychiatry, Virginia Commonwealth University, Richmond, VA 23219, USA
| | - Vladimir I. Vladimirov
- Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX 77807, USA
- Department of Psychiatry, College of Medicine, University of Arizona Phoenix, Phoenix, AZ 85004, USA
- Departent of Psychiatry, Virginia Commonwealth University, Richmond, VA 23219, USA
- Texas A&M Institute for Neuroscience, College Station, Texas A&M University, College Station, TX 77843, USA
- Genetics Interdisciplinary Program, College Station, Texas A&M University, College Station, TX 77843, USA
- Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD 21205, USA
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Sargazi S, Zahedi Abghari A, Mirinejad S, Heidari Nia M, Majidpour M, Danesh H, Saravani R, Sheervalilou R, Shakiba M, Zahedi Abghari F. Long noncoding RNA HOTAIR polymorphisms and susceptibility to bipolar disorder: a preliminary case-control study. NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS 2022; 41:684-701. [PMID: 35469536 DOI: 10.1080/15257770.2022.2065017] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Recent studies have shown that long noncoding RNAs contribute to the pathogenesis of bipolar disorder (BD). In this study, we genotyped four HOX Transcript Antisense Intergenic RNA (HOTAIR) gene polymorphisms to investigate if these variations could affect the risk of BD and its clinical subtypes. A total of 357 subjects, comprised of 194 BD patients and 163 age-matched healthy controls, were enrolled. Genotyping was carried out using PCR-RFLP and ARMS-PCR methods. We detected significant associations between the HOTAIR gene rs1899663 G/T, rs12826786 C/T, rs4759314 A/G, and rs920778 C/T polymorphism and the risk of BD under allelic, recessive, dominant, and codominant contrasted genetic models. The CT genotype of rs920778 C/T, GT genotype of rs1899663 G/T, and CT genotype of rs12826786 C/T polymorphisms enhanced the risk of BD type II (BDII). In contrast, the GG genotype of rs4759314 A/G polymorphism significantly diminished BDII risk by 83%. A positive association was noticed between CTTA and CTCG haplotypes of rs920778/rs1899663/rs12826786/rs4759314 and BD risk. Our findings reveal an interactive effect of HOTAIR polymorphisms on the development of BD and its subtypes. Further functional studies are needed to elucidate the role of these variations on HOTAIR expression and epigenetic status.
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Affiliation(s)
- Saman Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Armin Zahedi Abghari
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.,Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Shekoufeh Mirinejad
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Milad Heidari Nia
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Mahdi Majidpour
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.,Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Hiva Danesh
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Ramin Saravani
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.,Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | | | - Mansoor Shakiba
- Department of Psychiatry, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Fateme Zahedi Abghari
- Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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21
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Ortega MA, Fraile-Martínez Ó, García-Montero C, Alvarez-Mon MA, Lahera G, Monserrat J, Llavero-Valero M, Mora F, Rodríguez-Jiménez R, Fernandez-Rojo S, Quintero J, Alvarez De Mon M. Nutrition, Epigenetics, and Major Depressive Disorder: Understanding the Connection. Front Nutr 2022; 9:867150. [PMID: 35662945 PMCID: PMC9158469 DOI: 10.3389/fnut.2022.867150] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 04/19/2022] [Indexed: 12/12/2022] Open
Abstract
Major depressive disorder (MDD) is a complex, multifactorial disorder of rising prevalence and incidence worldwide. Nearly, 280 million of people suffer from this leading cause of disability in the world. Moreover, patients with this condition are frequently co-affected by essential nutrient deficiency. The typical scene with stress and hustle in developed countries tends to be accompanied by eating disorders implying overnutrition from high-carbohydrates and high-fat diets with low micronutrients intake. In fact, currently, coronavirus disease 2019 (COVID-19) pandemic has drawn more attention to this underdiagnosed condition, besides the importance of the nutritional status in shaping immunomodulation, in which minerals, vitamins, or omega 3 polyunsaturated fatty acids (ω-3 PUFA) play an important role. The awareness of nutritional assessment is greater and greater in the patients with depression since antidepressant treatments have such a significant probability of failing. As diet is considered a crucial environmental factor, underlying epigenetic mechanisms that experience an adaptation or consequence on their signaling and expression mechanisms are reviewed. In this study, we included metabolic changes derived from an impairment in cellular processes due to lacking some essential nutrients in diet and therefore in the organism. Finally, aspects related to nutritional interventions and recommendations are also addressed.
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Affiliation(s)
- Miguel A. Ortega
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Cancer Registry and Pathology Department, Hospital Universitario Principe de Asturias, Alcalá de Henares, Spain
- *Correspondence: Miguel A. Ortega
| | - Óscar Fraile-Martínez
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Cielo García-Montero
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Miguel Angel Alvarez-Mon
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - Guillermo Lahera
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, Madrid, Spain
- Psychiatry Service, Center for Biomedical Research in the Mental Health Network, University Hospital Príncipe de Asturias, Alcalá de Henares, Spain
| | - Jorge Monserrat
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Maria Llavero-Valero
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - Fernando Mora
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, Madrid, Spain
- Department of Legal Medicine and Psychiatry, Complutense University, Madrid, Spain
| | - Roberto Rodríguez-Jiménez
- Department of Legal Medicine and Psychiatry, Complutense University, Madrid, Spain
- Institute for Health Research 12 de Octubre Hospital, (Imas 12)/CIBERSAM (Biomedical Research Networking Centre in Mental Health), Madrid, Spain
| | - Sonia Fernandez-Rojo
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, Madrid, Spain
- Department of Legal Medicine and Psychiatry, Complutense University, Madrid, Spain
| | - Javier Quintero
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, Madrid, Spain
- Department of Legal Medicine and Psychiatry, Complutense University, Madrid, Spain
| | - Melchor Alvarez De Mon
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Immune System Diseases-Rheumatology, Oncology Service an Internal Medicine, University Hospital Príncipe de Asturias, (CIBEREHD), Alcalá de Henares, Spain
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22
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Hao WZ, Chen Q, Wang L, Tao G, Gan H, Deng LJ, Huang JQ, Chen JX. Emerging roles of long non-coding RNA in depression. Prog Neuropsychopharmacol Biol Psychiatry 2022; 115:110515. [PMID: 35077841 DOI: 10.1016/j.pnpbp.2022.110515] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 01/15/2022] [Accepted: 01/18/2022] [Indexed: 12/31/2022]
Abstract
Depression is the second most common psychiatric disorder, affecting more than 340 million people of all ages worldwide. However, the mechanisms underlying the development of depression remain unclear, and existing antidepressants may cause clinical dependence and toxic side effects. Recently, emerging evidence from the fields of neuroscience, genetics, and genomics supports the modulatory role of long non-coding RNA (lncRNA) in depression. LncRNAs may mediate the pathogenesis of depression through multiple pathways, including regulating neurotransmitters and neurotrophic factors, affecting synaptic conduction, and regulating the ventriculo-olfactory neurogenic system. In addition, relying on genome-wide association study and molecular biological experiment, the possibility of lncRNA as a potential biomarker for the differential diagnosis of depression and other mental illnesses, including schizophrenia and anxiety disorders, is gradually being revealed. Thus, it is important to explore whether lncRNAs are potential therapeutic targets and diagnostic biomarkers for depression. Here, we summarize the genesis and function of lncRNAs and discuss the aberrant expression and functional roles of lncRNAs in the development, diagnosis, and therapy of depression, as well as the deficiencies and limitations of these studies. Moreover, we established a lncRNA-miRNA-mRNA-pathway-drug network of depression through bioinformatics analysis methods to deepen our understanding of the relationship between lncRNA and depression, promoting the clinical application of epigenetic research.
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Affiliation(s)
- Wen-Zhi Hao
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Qian Chen
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Lu Wang
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Gabriel Tao
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, United States
| | - Hua Gan
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Li-Juan Deng
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Jun-Qing Huang
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
| | - Jia-Xu Chen
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
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23
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Ginsenoside Rg1 Reduced Microglial Activation and Mitochondrial Dysfunction to Alleviate Depression-Like Behaviour Via the GAS5/EZH2/SOCS3/NRF2 Axis. Mol Neurobiol 2022; 59:2855-2873. [PMID: 35230663 PMCID: PMC9016007 DOI: 10.1007/s12035-022-02740-7] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 01/07/2022] [Indexed: 12/31/2022]
Abstract
Ginsenoside Rg1 is the principal active ingredient in ginseng. The antidepressant effects of Rg1 have been validated; however, the specific underlying mechanism of this effect needs further research. Rats were subjected to the chronic restraint stress (CRS) depression model. Rg1, or a positive control drug, was administered to the rats. Depression-like behaviours were evaluated through behavioural experiments. Cytokine, mRNA, protein, ATP, and mitochondria DNA levels were detected using the indicated methods. Lentivirus-packaged plasmids were injected into the rat brain for GAS5 overexpression or knockdown. In vitro mitochondrial dysfunction was evaluated by detecting mitochondrial reactive oxygen species and mitochondrial membrane potential. Direct interaction between GAS5 and EZH2 was validated by RNA immunoprecipitation and RNA pull-down assay. The enrichment of EZH2 and H3K27me3 was evaluated through chromatin immunoprecipitation quantitative real-time PCR. Rg1 treatment alleviated depression-like behaviours, microglial activation, and mitochondrial dysfunction in CRS rats. Similarly, GAS5 knockdown revealed a similar protective effect of Rg1 treatment. GAS5 overexpression in the rat brain compromised the protective effect of Rg1 treatment. Moreover, Rg1 treatment or GAS5 knockdown attenuated microglial activation and mitochondrial dysfunction in vitro. Mechanically, GAS5 was suppressed SOCS3 and NRF2 expression by facilitating EZH2-mediated transcriptional repression. Rg1 attenuated microglial activation and improved mitochondrial dysfunction in depression by downregulating GAS5 expression. Mechanically, GAS5 might regulate microglial activation and mitochondrial dysfunction via the epigenetic suppression of NRF2 and SOCS3.
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24
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Jovčevska I, Videtič Paska A. Neuroepigenetics of psychiatric disorders: Focus on lncRNA. Neurochem Int 2021; 149:105140. [PMID: 34298078 DOI: 10.1016/j.neuint.2021.105140] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 07/16/2021] [Accepted: 07/18/2021] [Indexed: 01/01/2023]
Abstract
Understanding the pathology of psychiatric disorders is challenging due to their complexity and multifactorial origin. However, development of high-throughput technologies has allowed for better insight into their molecular signatures. Advancement of sequencing methodologies have made it possible to study not only the protein-coding but also the noncoding genome. It is now clear that besides the genetic component, different epigenetic mechanisms play major roles in the onset and development of psychiatric disorders. Among them, examining the role of long noncoding RNAs (lncRNAs) is a relatively new field. Here, we present an overview of what is currently known about the involvement of lncRNAs in schizophrenia, major depressive and bipolar disorders, as well as suicide. The diagnosis of psychiatric disorders mainly relies on clinical evaluation without using measurable biomarkers. In this regard, lncRNA may open new opportunities for development of molecular tests. However, so far only a small set of known lncRNAs have been characterized at molecular level, which means they have a long way to go before clinical implementation. Understanding how changes in lncRNAs affect the appearance and development of psychiatric disorders may lead to a more classified and objective diagnostic system, but also open up new therapeutic targets for these patients.
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Affiliation(s)
- Ivana Jovčevska
- Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia.
| | - Alja Videtič Paska
- Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia.
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25
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Zhang Z, Wu H, Peng Q, Xie Z, Chen F, Ma Y, Zhang Y, Zhou Y, Yang J, Chen C, Li S, Zhang Y, Tian W, Wang Y, Xu Y, Luo H, Zhu M, Kuang YQ, Yu J, Wang K. Integration of Molecular Inflammatory Interactome Analyses Reveals Dynamics of Circulating Cytokines and Extracellular Vesicle Long Non-Coding RNAs and mRNAs in Heroin Addicts During Acute and Protracted Withdrawal. Front Immunol 2021; 12:730300. [PMID: 34489980 PMCID: PMC8416766 DOI: 10.3389/fimmu.2021.730300] [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] [Received: 06/24/2021] [Accepted: 08/04/2021] [Indexed: 01/01/2023] Open
Abstract
Heroin addiction and withdrawal influence multiple physiological functions, including immune responses, but the mechanism remains largely elusive. The objective of this study was to investigate the molecular inflammatory interactome, particularly the cytokines and transcriptome regulatory network in heroin addicts undergoing withdrawal, compared to healthy controls (HCs). Twenty-seven cytokines were simultaneously assessed in 41 heroin addicts, including 20 at the acute withdrawal (AW) stage and 21 at the protracted withdrawal (PW) stage, and 38 age- and gender-matched HCs. Disturbed T-helper(Th)1/Th2, Th1/Th17, and Th2/Th17 balances, characterized by reduced interleukin (IL)-2, elevated IL-4, IL-10, and IL-17A, but normal TNF-α, were present in the AW subjects. These imbalances were mostly restored to the baseline at the PW stage. However, the cytokines TNF-α, IL-2, IL-7, IL-10, and IL-17A remained dysregulated. This study also profiled exosomal long non-coding RNA (lncRNA) and mRNA in the plasma of heroin addicts, constructed co-expression gene regulation networks, and identified lncRNA-mRNA-pathway pairs specifically associated with alterations in cytokine profiles and Th1/Th2/Th17 imbalances. Altogether, a large amount of cytokine and exosomal lncRNA/mRNA expression profiling data relating to heroin withdrawal was obtained, providing a useful experimental and theoretical basis for further understanding of the pathogenic mechanisms of withdrawal symptoms in heroin addicts.
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Affiliation(s)
- Zunyue Zhang
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Centre for Experimental Studies and Research, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Hongjin Wu
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Centre for Experimental Studies and Research, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Qingyan Peng
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Centre for Experimental Studies and Research, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Zhenrong Xie
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Fengrong Chen
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Centre for Experimental Studies and Research, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yuru Ma
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Centre for Experimental Studies and Research, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yizhi Zhang
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Centre for Experimental Studies and Research, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yong Zhou
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Jiqing Yang
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Centre for Experimental Studies and Research, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Cheng Chen
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Shaoyou Li
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Centre for Experimental Studies and Research, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yongjin Zhang
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Centre for Experimental Studies and Research, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Weiwei Tian
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yuan Wang
- Department of Research and Development, Echo Biotech Co., Ltd, Beijing, China
| | - Yu Xu
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Huayou Luo
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Mei Zhu
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yi-Qun Kuang
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Juehua Yu
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Centre for Experimental Studies and Research, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Kunhua Wang
- National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Centre for Experimental Studies and Research, The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, China.,Yunnan University, Kunming, China
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26
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Kawatake-Kuno A, Murai T, Uchida S. The Molecular Basis of Depression: Implications of Sex-Related Differences in Epigenetic Regulation. Front Mol Neurosci 2021; 14:708004. [PMID: 34276306 PMCID: PMC8282210 DOI: 10.3389/fnmol.2021.708004] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 06/14/2021] [Indexed: 12/22/2022] Open
Abstract
Major depressive disorder (MDD) is a leading cause of disability worldwide. Although the etiology and pathophysiology of MDD remain poorly understood, aberrant neuroplasticity mediated by the epigenetic dysregulation of gene expression within the brain, which may occur due to genetic and environmental factors, may increase the risk of this disorder. Evidence has also been reported for sex-related differences in the pathophysiology of MDD, with female patients showing a greater severity of symptoms, higher degree of functional impairment, and more atypical depressive symptoms. Males and females also differ in their responsiveness to antidepressants. These clinical findings suggest that sex-dependent molecular and neural mechanisms may underlie the development of depression and the actions of antidepressant medications. This review discusses recent advances regarding the role of epigenetics in stress and depression. The first section presents a brief introduction of the basic mechanisms of epigenetic regulation, including histone modifications, DNA methylation, and non-coding RNAs. The second section reviews their contributions to neural plasticity, the risk of depression, and resilience against depression, with a particular focus on epigenetic modulators that have causal relationships with stress and depression in both clinical and animal studies. The third section highlights studies exploring sex-dependent epigenetic alterations associated with susceptibility to stress and depression. Finally, we discuss future directions to understand the etiology and pathophysiology of MDD, which would contribute to optimized and personalized therapy.
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Affiliation(s)
- Ayako Kawatake-Kuno
- SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Toshiya Murai
- SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.,Department of Psychiatry, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Shusaku Uchida
- SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
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27
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Bu T, Qiao Z, Wang W, Yang X, Zhou J, Chen L, Yang J, Xu J, Ji Y, Wang Y, Zhang W, Yang Y, Qiu X, Yu Y. Diagnostic Biomarker Hsa_circ_0126218 and Functioning Prediction in Peripheral Blood Monocular Cells of Female Patients With Major Depressive Disorder. Front Cell Dev Biol 2021; 9:651803. [PMID: 34095115 PMCID: PMC8174117 DOI: 10.3389/fcell.2021.651803] [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] [Received: 01/11/2021] [Accepted: 03/22/2021] [Indexed: 12/22/2022] Open
Abstract
Introduction Although major depressive diroder (MDD) has brought huge burden and challenges to society globally, effective and accurate diagnoses and treatments remain inadequate. The pathogenesis that for women are more likely to suffer from depression than men needs to be excavated as well. The function of circRNAs in pathological process of depression has not been widely investigated. This study aims to explore potential diagnostic biomarker circRNA of female patients with MDD and to investigate its role in pathogenesis. Methods First, an expression profile of circRNAs in the peripheral blood monocular cells of MDD patients and healthy peripherals were established based on high-throughput sequencing analysis. In addition, the top 10 differentially expressed circRNAs were quantified by quantitative real-time PCR to explore diagnostic biomarkers. To further investigate the function of biomarkers in the pathogenesis of MDD, bioinformatics analysis on downstream target genes of the biomarkers was carried out. Results There is a mass of dysregulated circRNAs in PBMCs between female MDD patients and healthy controls. Among the top 10 differentially expressed circRNAs, hsa_circ_0126218 is more feasible as a diagnostic biomarker. The expression level of hsa_circ_0126218 displayed upregulation in patients with MDD and the area under the operating characteristic curve of hsa_circ_0126218 was 0.801 (95% CI 0.7226–0.8791, p < 0.0001). To explain the competing endogenous RNA role of hsa_circ_0126218 in the pathogenesis of female MDD, a hsa_circ_0126218-miRNA-mRNA network was established. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses stated that some of the enriched pathways downstream of hsa_circ_0126218 are closely related to MDD. Moreover, we established a protein-protein network to further screen out the hub genes (PIK3CA, PTEN, MAPK1, CDC42, Lyn, YES1, EPHB2, SMAD2, STAT1, and ILK). The function of hsa_circ_0126218 was refined by constructing a verified circRNA-predicted miRNA-hub gene subnetwork. Conclusion hsa_circ_0126218 can be considered as a new female MDD biomarker, and the pathogenesis of female MDD by the downstream regulation of hsa_circ_0126218 has been predicted. These findings may help further improve the early detection, effective diagnosis, convenient monitoring of complications, precise treatment, and timely recurrence prevention of depression.
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Affiliation(s)
- Tianyi Bu
- Psychology and Health Management Center, Harbin Medical University, Harbin, China
| | - Zhengxue Qiao
- Psychology and Health Management Center, Harbin Medical University, Harbin, China
| | - Wenbo Wang
- Psychology and Health Management Center, Harbin Medical University, Harbin, China
| | - Xiuxian Yang
- Psychology and Health Management Center, Harbin Medical University, Harbin, China
| | - Jiawei Zhou
- Psychology and Health Management Center, Harbin Medical University, Harbin, China
| | - Lu Chen
- Department of Endocrinology, Peking Union Medical College Hospital, Beijing, China
| | - Jiarun Yang
- Psychology and Health Management Center, Harbin Medical University, Harbin, China
| | - Jia Xu
- Psychotherapy Department, The First Psychiatric Hospital of Harbin, Harbin, China
| | - Yanping Ji
- Department of Nursing, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yini Wang
- Psychology and Health Management Center, Harbin Medical University, Harbin, China
| | - Wenxin Zhang
- Medical Department, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yanjie Yang
- Psychology and Health Management Center, Harbin Medical University, Harbin, China
| | - Xiaohui Qiu
- Psychology and Health Management Center, Harbin Medical University, Harbin, China
| | - Yunmiao Yu
- Psychology and Health Management Center, Harbin Medical University, Harbin, China
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28
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Hussen BM, Azimi T, Hidayat HJ, Taheri M, Ghafouri-Fard S. Long Non-coding RNA RMRP in the Pathogenesis of Human Disorders. Front Cell Dev Biol 2021; 9:676588. [PMID: 33996836 PMCID: PMC8120005 DOI: 10.3389/fcell.2021.676588] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 04/12/2021] [Indexed: 12/17/2022] Open
Abstract
RNA component of mitochondrial RNA processing endoribonuclease (RMRP) is a non-coding transcript firstly acknowledged for its association with the cartilage-hair hypoplasia (CHH) syndrome, a rare autosomal recessive condition. This transcript has been spotted in both nucleus and mitochondria. In addition to its role in the pathogenesis of CHH, RMRP participates in the pathogenesis of cancers. Independent studies in bladder cancer, colon cancer, hepatocellular carcinoma, lung cancer, breast carcinoma and multiple myeloma have confirmed the oncogenic effects of RMRP. Mechanistically, RMRP serves as a sponge for some miRNAs such as miR-206, miR-613, and miR-217. In addition to these miRNAs, expressions of tens of miRNAs have been altered following RMRP silencing, implying the vast extent of RMRP/miRNA network. In the present narrative review, we explain the role of RMRP in the development of cancers and some other non-malignant disorders.
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Affiliation(s)
- Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Iraq
| | - Tahereh Azimi
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hazha Jamal Hidayat
- Department of Biology, College of Education, Salahadddin University-Erbil, Erbil, Iraq
| | - Mohammad Taheri
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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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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30
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Wu Y, Rong W, Jiang Q, Wang R, Huang H. Downregulation of lncRNA GAS5 Alleviates Hippocampal Neuronal Damage in Mice with Depression-Like Behaviors Via Modulation of MicroRNA-26a/EGR1 Axis. J Stroke Cerebrovasc Dis 2021; 30:105550. [PMID: 33341564 DOI: 10.1016/j.jstrokecerebrovasdis.2020.105550] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 12/07/2020] [Accepted: 12/09/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Accumulating evidences have demonstrated the roles of several long non-coding RNAs (lncRNAs) in depression. We aim to examine the capabilities of lncRNA growth arrest-specific transcript 5 (GAS5) on mice with depression-like behaviors and the mechanism of action. METHODS Fifty-six healthy mice were selected for model establishment. Morris water maze test and trapeze test were performed for evaluating learning and memory ability. The binding relationship between lncRNA GAS5 and microRNA-26a (miR-26a) and the target relationship between miR-26a and EGR1 were verified by dual-luciferase reporter gene assay. The apoptosis of neurons in the hippocampal CA1 region of mice was detected by TUNEL staining. The expression of inflammatory factors, lncRNA GAS5, miR-26a, early growth response gene 1 (EGR1), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway- and apoptosis-related factors in hippocampal tissues was tested by RT-qPCR and western blot analysis. RESULTS miR-26a expression was down-regulated while EGR1 and lncRNA GAS5 expression were up-regulated in hippocampal tissues of mice with depression-like behaviors. LncRNA GAS5 specifically bound to miR-26a and miR-26a targeted EGR1. Silencing of lncRNA GAS5 curtailed the release of inflammatory factors and the apoptosis of hippocampal neuron of mice with depression-like behaviors. EGR1 suppressed PI3K/AKT pathway activation to promote the release of inflammatory factors and the apoptosis of hippocampal neurons in mice with depression-like behaviors. CONCLUSION Our study provides evidence that silencing of lncRNA GAS5 could activate PI3K/AKT pathway to protect hippocampal neurons against damage in mice with depression-like behaviors by regulating the miR-26a/EGR1 axis.
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Affiliation(s)
- Yigao Wu
- Department of Medical Psychology, The First Affiliated Hospital of Wannan Medical College, No. 2, Zheshan West Road, Wuhu 241001, Anhui, PR China.
| | - Wei Rong
- Department of Clinical Medical Psychology, The Second People's Hospital of Wuhu, Wuhu 241001, Anhui, PR China.
| | - Qin Jiang
- Department of Medical Psychology, The First Affiliated Hospital of Wannan Medical College, No. 2, Zheshan West Road, Wuhu 241001, Anhui, PR China.
| | - Ruiquan Wang
- Department of Medical Psychology, The First Affiliated Hospital of Wannan Medical College, No. 2, Zheshan West Road, Wuhu 241001, Anhui, PR China.
| | - Huilan Huang
- Department of Medical Psychology, The First Affiliated Hospital of Wannan Medical College, No. 2, Zheshan West Road, Wuhu 241001, Anhui, PR China.
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31
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Simchovitz-Gesher A, Soreq H. Pharmaceutical Implications of Sex-Related RNA Divergence in Psychiatric Disorders. Trends Pharmacol Sci 2020; 41:840-850. [DOI: 10.1016/j.tips.2020.09.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 08/29/2020] [Accepted: 09/10/2020] [Indexed: 02/08/2023]
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32
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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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33
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Issler O, van der Zee YY, Ramakrishnan A, Wang J, Tan C, Loh YHE, Purushothaman I, Walker DM, Lorsch ZS, Hamilton PJ, Peña CJ, Flaherty E, Hartley BJ, Torres-Berrío A, Parise EM, Kronman H, Duffy JE, Estill MS, Calipari ES, Labonté B, Neve RL, Tamminga CA, Brennand KJ, Dong Y, Shen L, Nestler EJ. Sex-Specific Role for the Long Non-coding RNA LINC00473 in Depression. Neuron 2020; 106:912-926.e5. [PMID: 32304628 PMCID: PMC7305959 DOI: 10.1016/j.neuron.2020.03.023] [Citation(s) in RCA: 107] [Impact Index Per Article: 21.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 01/27/2020] [Accepted: 03/23/2020] [Indexed: 12/26/2022]
Abstract
Depression is a common disorder that affects women at twice the rate of men. Here, we report that long non-coding RNAs (lncRNAs), a recently discovered class of regulatory transcripts, represent about one-third of the differentially expressed genes in the brains of depressed humans and display complex region- and sex-specific patterns of regulation. We identified the primate-specific, neuronal-enriched gene LINC00473 as downregulated in prefrontal cortex (PFC) of depressed females but not males. Using viral-mediated gene transfer to express LINC00473 in adult mouse PFC neurons, we mirrored the human sex-specific phenotype by inducing stress resilience solely in female mice. This sex-specific phenotype was accompanied by changes in synaptic function and gene expression selectively in female mice and, along with studies of human neuron-like cells in culture, implicates LINC00473 as a CREB effector. Together, our studies identify LINC00473 as a female-specific driver of stress resilience that is aberrant in female depression.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Animals
- Behavior, Animal
- Depression/genetics
- Depression/metabolism
- Depressive Disorder, Major/genetics
- Depressive Disorder, Major/metabolism
- Down-Regulation
- Female
- Humans
- Male
- Mice
- Mice, Transgenic
- Middle Aged
- Neurons/metabolism
- Prefrontal Cortex/metabolism
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/metabolism
- RNA-Seq
- Resilience, Psychological
- Sex Factors
- Stress, Psychological/genetics
- Stress, Psychological/metabolism
- Young Adult
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Affiliation(s)
- Orna Issler
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Yentl Y van der Zee
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University, 6229 ER, Maastricht, the Netherlands
| | - Aarthi Ramakrishnan
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Junshi Wang
- Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Chunfeng Tan
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Yong-Hwee E Loh
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Immanuel Purushothaman
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Deena M Walker
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Zachary S Lorsch
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Peter J Hamilton
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Catherine J Peña
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Erin Flaherty
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Brigham J Hartley
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Angélica Torres-Berrío
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Eric M Parise
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Hope Kronman
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Julia E Duffy
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Molly S Estill
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Erin S Calipari
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Benoit Labonté
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Rachael L Neve
- Gene Delivery Technology Core, Massachusetts General Hospital, Cambridge, MA 02139, USA
| | - Carol A Tamminga
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Kristen J Brennand
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Yan Dong
- Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Li Shen
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Eric J Nestler
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
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