|
1
|
Al-Dahimavi S, Safaralizadeh R, Khalaj-Kondori M. Evaluating the Serum Level of ACTH and Investigating the Expression of miR-26a, miR-34a, miR-155-5p, and miR-146a in the Peripheral Blood Cells of Multiple Sclerosis Patients. Biochem Genet 2024:10.1007/s10528-024-10909-z. [PMID: 39223335 DOI: 10.1007/s10528-024-10909-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 08/23/2024] [Indexed: 09/04/2024]
Abstract
Multiple sclerosis (MS) is an inflammatory and neurodegenerative disorder affecting white and gray matter. This study aimed to investigate the association between clinical outcomes in MS patients and the levels of certain molecules in their serum, including ACTH, IL-17, and specific miRNAs: miR-26a, miR-34a, miR-155-5p, and miR-146a. Fifty healthy people and 75 blood samples from MS patients were selected. MS patients had higher expression levels of IL-17, miR-26a, miR-34a, and miR-146a compared to healthy individuals (p < 0.0001). There was no significant difference in miR-155-5p expression between the two groups (p = 0.203). MS patients also had higher serum levels of ACTH compared to the normal population (p < 0.0001). In MS patients, there was a negative correlation between IL-17 and miR-155-5p expression levels (p = 0.048, r = - 0.229). Similarly, a significant negative correlation was observed between ACTH and miR-155-5p in the control group (p = 0.044, r = - 0.286). The study's analysis revealed no significant difference in the expression of miR-155-5p between MS patients and normal individuals; the study's examination revealed that the expression level of IL-17, miR-26a, miR-34a, and miR-146a was higher in MS patients than in normal individuals.
Collapse
Affiliation(s)
- Sareh Al-Dahimavi
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Reza Safaralizadeh
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
| | - Mohammad Khalaj-Kondori
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| |
Collapse
|
|
2
|
Mafi A, Mannani R, Khalilollah S, Hedayati N, Salami R, Rezaee M, Dehmordi RM, Ghorbanhosseini SS, Alimohammadi M, Akhavan-Sigari R. The Significant Role of microRNAs in Gliomas Angiogenesis: A Particular Focus on Molecular Mechanisms and Opportunities for Clinical Application. Cell Mol Neurobiol 2023; 43:3277-3299. [PMID: 37414973 PMCID: PMC11409989 DOI: 10.1007/s10571-023-01385-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 06/25/2023] [Indexed: 07/08/2023]
Abstract
MicroRNAs (miRNAs) are non-coding RNAs with only 20-22 nucleic acids that inhibit gene transcription and translation by binding to mRNA. MiRNAs have a diverse set of target genes and can alter most physiological processes, including cell cycle checkpoints, cell survival, and cell death mechanisms, affecting the growth, development, and invasion of various cancers, including gliomas. So optimum management of miRNA expression is essential for preserving a normal biological environment. Due to their small size, stability, and capability of specifically targeting oncogenes, miRNAs have emerged as a promising marker and new biopharmaceutical targeted therapy for glioma patients. This review focuses on the most common miRNAs associated with gliomagenesis and development by controlling glioma-determining markers such as angiogenesis. We also summarized the recent research about miRNA effects on signaling pathways, their mechanistic role and cellular targets in the development of gliomas angiogenesis. Strategies for miRNA-based therapeutic targets, as well as limitations in clinical applications, are also discussed.
Collapse
Affiliation(s)
- Alireza Mafi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
- Nutrition and Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Reza Mannani
- Department of Surgery, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Shayan Khalilollah
- Department of Neurosurgery, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Neda Hedayati
- School of Medicine, Iran University of Medical Science, Tehran, Iran
| | - Raziyeh Salami
- Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Malihe Rezaee
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Rohollah Mousavi Dehmordi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
- Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyedeh Sara Ghorbanhosseini
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mina Alimohammadi
- Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Reza Akhavan-Sigari
- Department of Neurosurgery, University Medical Center Tuebingen, Tübingen, Germany
- Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw Management University Warsaw, Warsaw, Poland
| |
Collapse
|
|
3
|
Shyamasundar S, Ramya S, Kandilya D, Srinivasan DK, Bay BH, Ansari SA, Dheen ST. Maternal Diabetes Deregulates the Expression of Mecp2 via miR-26b-5p in Mouse Embryonic Neural Stem Cells. Cells 2023; 12:1516. [PMID: 37296636 PMCID: PMC10252249 DOI: 10.3390/cells12111516] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 05/22/2023] [Accepted: 05/22/2023] [Indexed: 06/12/2023] Open
Abstract
Maternal diabetes has been associated with a greater risk of neurodevelopmental disorders in offspring. It has been established that hyperglycemia alters the expression of genes and microRNAs (miRNAs) regulating the fate of neural stem cells (NSCs) during brain development. In this study, the expression of methyl-CpG-binding protein-2 (Mecp2), a global chromatin organizer and a crucial regulator of synaptic proteins, was analyzed in NSCs obtained from the forebrain of embryos of diabetic mice. Mecp2 was significantly downregulated in NSCs derived from embryos of diabetic mice when compared to controls. miRNA target prediction revealed that the miR-26 family could regulate the expression of Mecp2, and further validation confirmed that Mecp2 is a target of miR-26b-5p. Knockdown of Mecp2 or overexpression of miR-26b-5p altered the expression of tau protein and other synaptic proteins, suggesting that miR-26b-5p alters neurite outgrowth and synaptogenesis via Mecp2. This study revealed that maternal diabetes upregulates the expression of miR-26b-5p in NSCs, resulting in downregulation of its target, Mecp2, which in turn perturbs neurite outgrowth and expression of synaptic proteins. Overall, hyperglycemia dysregulates synaptogenesis that may manifest as neurodevelopmental disorders in offspring from diabetic pregnancy.
Collapse
Affiliation(s)
- Sukanya Shyamasundar
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore
| | - Seshadri Ramya
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore
| | - Deepika Kandilya
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore
| | - Dinesh Kumar Srinivasan
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore
| | - Boon Huat Bay
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore
| | - Suraiya Anjum Ansari
- Department of Biochemistry and Molecular Biology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
| | - S Thameem Dheen
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore
| |
Collapse
|
|
4
|
Botelho ME, Lopes MS, Mathur PK, Knol EF, e Silva FF, Lopes PS, Gimarães SEF, Marques DB, Veroneze R. Weighted genome-wide association study reveals new candidate genes related to boar taint compounds 1. Livest Sci 2022. [DOI: 10.1016/j.livsci.2022.104845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
|
|
5
|
Barut Z, Cabbar AT, Yilmaz SG, Akdeniz FT, Simsek MA, Capar B, Degertekin M, Dalan AB, Yerebakan H, Isbir T. Investigation of Circulating miRNA-133, miRNA-26, and miRNA-378 as Candidate Biomarkers for Left Ventricular Hypertrophy. In Vivo 2021; 35:1605-1610. [PMID: 33910842 DOI: 10.21873/invivo.12417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 02/04/2021] [Accepted: 02/11/2021] [Indexed: 11/10/2022]
Abstract
BACKGROUND/AIM Left ventricular hypertrophy (LVH) involves increased muscular mass of the left ventricle due to increased cardiomyocyte size and is caused by cardiomyopathies. Several microRNAs (miRNAs) have been implicated in processes that contribute to heart disease. This study aimed to examine miRNA-133, miRNA-26 and miRNA-378 as candidate biomarkers to define prognosis in patients with LVH. PATIENTS AND METHODS The study group consisted of 70 patients who were diagnosed with LVH and 16 unaffected individuals who served as the control group. Real-time polymerase chain reaction (RT-PCR) was used to analyze serum miRNA-133, miRNA-26, and miRNA-378 expression levels in LVH patients and the control group. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic capability of miRNA-378. RESULTS When crossing threshold (CT) values were compared between patient and control samples, we found that there were no statistically significant differences in miRNA-133 and miRNA-26 CT values, while the miRNA-378 expression was significantly increased in LVH patients. ROC analysis demonstrated that the expression levels of miRNA-378 (AUC=0.484, p=0.0013) were significantly different between groups. CONCLUSION We observed a statistically significant relationship between miRNA-378 expression levels and LVH, suggesting that circulating miRNA-378 may be used as a novel biomarker to distinguish patients who have LVH from those who do not.
Collapse
Affiliation(s)
- Zerrin Barut
- Department of Basic Medical Science, Faculty of Dentistry, Antalya Bilim University, Antalya, Turkey
| | - Ayca Turer Cabbar
- Department of Cardiology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
| | - Seda Gulec Yilmaz
- Department of Medical Biology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
| | - Fatma Tuba Akdeniz
- Department of Medical Biology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
| | - Mustafa Aytek Simsek
- Department of Cardiology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
| | - Betul Capar
- Department of Molecular Medicine, Institute of Health Sciences, Yeditepe University, Istanbul, Turkey
| | - Muzaffer Degertekin
- Department of Cardiology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
| | - Altay Burak Dalan
- Department of Medical Biology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
| | - Halit Yerebakan
- Department of Cardiovascular Surgery, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
| | - Turgay Isbir
- Department of Medical Biology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey;
| |
Collapse
|
|
6
|
Sauer M, Was N, Ziegenhals T, Wang X, Hafner M, Becker M, Fischer U. The miR-26 family regulates neural differentiation-associated microRNAs and mRNAs by directly targeting REST. J Cell Sci 2021; 134:jcs257535. [PMID: 34151974 PMCID: PMC11443607 DOI: 10.1242/jcs.257535] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 05/11/2021] [Indexed: 01/13/2023] Open
Abstract
Repressor element 1-silencing transcription factor (REST) plays a crucial role in the differentiation of neural progenitor cells (NPCs). C-terminal domain small phosphatases (CTDSPs) are REST effector proteins that reduce RNA polymerase II activity on genes required for neurogenesis. miR-26b regulates neurogenesis in zebrafish by targeting ctdsp2 mRNA, but the molecular events triggered by this microRNA (miR) remain unknown. Here, we show in a murine embryonic stem cell differentiation paradigm that inactivation of miR-26 family members disrupts the formation of neurons and astroglia and arrests neurogenesis at the neural progenitor level. Furthermore, we show that miR-26 directly targets Rest, thereby inducing the expression of a large set of REST complex-repressed neuronal genes, including miRs required for induction of the neuronal gene expression program. Our data identify the miR-26 family as the trigger of a self-amplifying system required for neural differentiation that acts upstream of REST-controlled miRs.
Collapse
Affiliation(s)
- Mark Sauer
- Institute for Medical Radiology and Cell Research (MSZ) in the Center for Experimental Molecular Medicine (ZEMM), University of Würzburg, D-97078 Würzburg, Germany
| | - Nina Was
- Institute for Medical Radiology and Cell Research (MSZ) in the Center for Experimental Molecular Medicine (ZEMM), University of Würzburg, D-97078 Würzburg, Germany
| | - Thomas Ziegenhals
- Department of Biochemistry, Theodor Boveri-Institute, University of Würzburg, D-97074 Würzburg, Germany
| | - Xiantao Wang
- RNA Molecular Biology Group, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Disease, Bethesda, MD 20892, USA
| | - Markus Hafner
- RNA Molecular Biology Group, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Disease, Bethesda, MD 20892, USA
| | - Matthias Becker
- Institute for Medical Radiology and Cell Research (MSZ) in the Center for Experimental Molecular Medicine (ZEMM), University of Würzburg, D-97078 Würzburg, Germany
| | - Utz Fischer
- Department of Biochemistry, Theodor Boveri-Institute, University of Würzburg, D-97074 Würzburg, Germany
| |
Collapse
|
|
7
|
Herbst F, Lang TJL, Eckert ESP, Wünsche P, Wurm AA, Kindinger T, Laaber K, Hemmati S, Hotz-Wagenblatt A, Zavidij O, Paruzynski A, Lu J, von Kalle C, Zenz T, Klein C, Schmidt M, Ball CR, Glimm H. The balance between the intronic miR-342 and its host gene Evl determines hematopoietic cell fate decision. Leukemia 2021; 35:2948-2963. [PMID: 34021250 PMCID: PMC8478659 DOI: 10.1038/s41375-021-01267-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 04/06/2021] [Accepted: 04/27/2021] [Indexed: 02/06/2023]
Abstract
Protein-coding and non-coding genes like miRNAs tightly control hematopoietic differentiation programs. Although miRNAs are frequently located within introns of protein-coding genes, the molecular interplay between intronic miRNAs and their host genes is unclear. By genomic integration site mapping of gamma-retroviral vectors in genetically corrected peripheral blood from gene therapy patients, we identified the EVL/MIR342 gene locus as a hotspot for therapeutic vector insertions indicating its accessibility and expression in human hematopoietic stem and progenitor cells. We therefore asked if and how EVL and its intronic miRNA-342 regulate hematopoiesis. Here we demonstrate that overexpression (OE) of Evl in murine primary Lin- Sca1+ cKit+ cells drives lymphopoiesis whereas miR-342 OE increases myeloid colony formation in vitro and in vivo, going along with a profound upregulation of canonical pathways essential for B-cell development or myelopoietic functions upon Evl or miR-342 OE, respectively. Strikingly, miR-342 counteracts its host gene by targeting lymphoid signaling pathways, resulting in reduced pre-B-cell output. Moreover, EVL overexpression is associated with lymphoid leukemia in patients. In summary, our data show that one common gene locus regulates distinct hematopoietic differentiation programs depending on the gene product expressed, and that the balance between both may determine hematopoietic cell fate decision.
Collapse
Affiliation(s)
- Friederike Herbst
- grid.461742.2Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Tonio J. L. Lang
- grid.461742.2Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany ,grid.6363.00000 0001 2218 4662Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Tumorimmunology, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Elias S. P. Eckert
- grid.461742.2Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany ,grid.7700.00000 0001 2190 4373Faculty of Biosciences, University Heidelberg, 69120 Heidelberg, Germany
| | - Peer Wünsche
- grid.461742.2Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany ,grid.7700.00000 0001 2190 4373Faculty of Biosciences, University Heidelberg, 69120 Heidelberg, Germany
| | - Alexander A. Wurm
- grid.4488.00000 0001 2111 7257Mildred Scheel Early Career Center, National Center for Tumor Diseases Dresden (NCT/UCC), Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany ,grid.461742.2Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), 01307 Dresden, Germany ,grid.4488.00000 0001 2111 7257Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus Dresden at TU Dresden, 01307 Dresden, Germany
| | - Tim Kindinger
- grid.461742.2Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Karin Laaber
- grid.461742.2Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany ,grid.7700.00000 0001 2190 4373Faculty of Biosciences, University Heidelberg, 69120 Heidelberg, Germany
| | - Shayda Hemmati
- grid.461742.2Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany ,grid.7700.00000 0001 2190 4373Faculty of Biosciences, University Heidelberg, 69120 Heidelberg, Germany
| | - Agnes Hotz-Wagenblatt
- grid.7497.d0000 0004 0492 0584Omics IT and Data Management Core Facility, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Oksana Zavidij
- grid.461742.2Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | | | - Junyan Lu
- grid.4709.a0000 0004 0495 846XEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany
| | - Christof von Kalle
- grid.461742.2Department of Translational Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany ,GeneWerk GmbH, 69120 Heidelberg, Germany ,grid.7497.d0000 0004 0492 0584German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
| | - Thorsten Zenz
- grid.412004.30000 0004 0478 9977Department of Medical Oncology and Haematology, University Hospital Zurich & University of Zurich, 8091 Zurich, Switzerland
| | - Christoph Klein
- grid.411095.80000 0004 0477 2585Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, 80337 Munich, Germany
| | - Manfred Schmidt
- grid.461742.2Department of Translational Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany ,GeneWerk GmbH, 69120 Heidelberg, Germany
| | - Claudia R. Ball
- grid.461742.2Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), 01307 Dresden, Germany ,grid.4488.00000 0001 2111 7257Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus Dresden at TU Dresden, 01307 Dresden, Germany ,grid.7497.d0000 0004 0492 0584German Cancer Consortium (DKTK), 01307 Dresden, Germany
| | - Hanno Glimm
- grid.461742.2Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany ,grid.461742.2Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), 01307 Dresden, Germany ,grid.4488.00000 0001 2111 7257Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus Dresden at TU Dresden, 01307 Dresden, Germany ,grid.7497.d0000 0004 0492 0584German Cancer Consortium (DKTK), 01307 Dresden, Germany
| |
Collapse
|
|
8
|
Tini G, Varma V, Lombardo R, Nolen GT, Lefebvre G, Descombes P, Métairon S, Priami C, Kaput J, Scott-Boyer MP. DNA methylation during human adipogenesis and the impact of fructose. GENES AND NUTRITION 2020; 15:21. [PMID: 33243154 PMCID: PMC7691080 DOI: 10.1186/s12263-020-00680-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 11/10/2020] [Indexed: 01/12/2023]
Abstract
BACKGROUND Increased adipogenesis and altered adipocyte function contribute to the development of obesity and associated comorbidities. Fructose modified adipocyte metabolism compared to glucose, but the regulatory mechanisms and consequences for obesity are unknown. Genome-wide methylation and global transcriptomics in SGBS pre-adipocytes exposed to 0, 2.5, 5, and 10 mM fructose, added to a 5-mM glucose-containing medium, were analyzed at 0, 24, 48, 96, 192, and 384 h following the induction of adipogenesis. RESULTS Time-dependent changes in DNA methylation compared to baseline (0 h) occurred during the final maturation of adipocytes, between 192 and 384 h. Larger percentages (0.1% at 192 h, 3.2% at 384 h) of differentially methylated regions (DMRs) were found in adipocytes differentiated in the glucose-containing control media compared to adipocytes differentiated in fructose-supplemented media (0.0006% for 10 mM, 0.001% for 5 mM, and 0.005% for 2.5 mM at 384 h). A total of 1437 DMRs were identified in 5237 differentially expressed genes at 384 h post-induction in glucose-containing (5 mM) control media. The majority of them inversely correlated with the gene expression, but 666 regions were positively correlated to the gene expression. CONCLUSIONS Our studies demonstrate that DNA methylation regulates or marks the transformation of morphologically differentiating adipocytes (seen at 192 h), to the more mature and metabolically robust adipocytes (as seen at 384 h) in a genome-wide manner. Lower (2.5 mM) concentrations of fructose have the most robust effects on methylation compared to higher concentrations (5 and 10 mM), suggesting that fructose may be playing a signaling/regulatory role at lower concentrations of fructose and as a substrate at higher concentrations.
Collapse
Affiliation(s)
- Giulia Tini
- The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Piazza Manifattura 1, 38068, Rovereto, Italy.,Department of Mathematics, University of Trento, Via Sommarive 14, 38050, Povo, Italy.,Present address: Department of Experimental Oncology, IEO European Institute of Oncology IRCSS, Milan, Italy
| | - Vijayalakshmi Varma
- Division of Systems Biology, National Center for Toxicological Research, FDA, 3900 NCTR Road, Jefferson, AR, 72079, USA.,Present Address: Cardiovascular Renal and Metabolism Division of MedImmune, Astrazeneca, Gaithersburg, MD, 20878, USA
| | - Rosario Lombardo
- The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Piazza Manifattura 1, 38068, Rovereto, Italy
| | - Greg T Nolen
- Division of Systems Biology, National Center for Toxicological Research, FDA, 3900 NCTR Road, Jefferson, AR, 72079, USA
| | | | | | | | - Corrado Priami
- The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Piazza Manifattura 1, 38068, Rovereto, Italy.,Department of Computer Science, University of Pisa, Pisa, Italy
| | - Jim Kaput
- Nestlé Institute of Health Science, Lausanne, Switzerland.,Present Addresses: Vydiant Inc., Folsom, CA, 95630, USA
| | - Marie-Pier Scott-Boyer
- The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Piazza Manifattura 1, 38068, Rovereto, Italy. .,Present Address: CRCHU de Québec-Université Laval, Quebec City, Québec, Canada.
| |
Collapse
|
|
9
|
Rajabi H, Aslani S, Abhari A, Sanajou D. Expression Profiles of MicroRNAs in Stem Cells Differentiation. Curr Pharm Biotechnol 2020; 21:906-918. [PMID: 32072899 DOI: 10.2174/1389201021666200219092520] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 12/06/2019] [Accepted: 02/06/2020] [Indexed: 12/12/2022]
Abstract
Stem cells are undifferentiated cells and have a great potential in multilineage differentiation. These cells are classified into adult stem cells like Mesenchymal Stem Cells (MSCs) and Embryonic Stem Cells (ESCs). Stem cells also have potential therapeutic utility due to their pluripotency, self-renewal, and differentiation ability. These properties make them a suitable choice for regenerative medicine. Stem cells differentiation toward functional cells is governed by different signaling pathways and transcription factors. Recent studies have demonstrated the key role of microRNAs in the pathogenesis of various diseases, cell cycle regulation, apoptosis, aging, cell fate decisions. Several types of stem cells have different and unique miRNA expression profiles. Our review summarizes novel regulatory roles of miRNAs in the process of stem cell differentiation especially adult stem cells into a variety of functional cells through signaling pathways and transcription factors modulation. Understanding the mechanistic roles of miRNAs might be helpful in elaborating clinical therapies using stem cells and developing novel biomarkers for the early and effective diagnosis of pathologic conditions.
Collapse
Affiliation(s)
- Hadi Rajabi
- Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Somayeh Aslani
- Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Abhari
- Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Davoud Sanajou
- Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
|
10
|
Ferro E, Enrico Bena C, Grigolon S, Bosia C. From Endogenous to Synthetic microRNA-Mediated Regulatory Circuits: An Overview. Cells 2019; 8:E1540. [PMID: 31795372 PMCID: PMC6952906 DOI: 10.3390/cells8121540] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 11/22/2019] [Accepted: 11/25/2019] [Indexed: 12/13/2022] Open
Abstract
MicroRNAs are short non-coding RNAs that are evolutionarily conserved and are pivotal post-transcriptional mediators of gene regulation. Together with transcription factors and epigenetic regulators, they form a highly interconnected network whose building blocks can be classified depending on the number of molecular species involved and the type of interactions amongst them. Depending on their topology, these molecular circuits may carry out specific functions that years of studies have related to the processing of gene expression noise. In this review, we first present the different over-represented network motifs involving microRNAs and their specific role in implementing relevant biological functions, reviewing both theoretical and experimental studies. We then illustrate the recent advances in synthetic biology, such as the construction of artificially synthesised circuits, which provide a controlled tool to test experimentally the possible microRNA regulatory tasks and constitute a starting point for clinical applications.
Collapse
Affiliation(s)
- Elsi Ferro
- IIGM—Italian Institute for Genomic Medicine, c/o IRCCS, 10060 Candiolo (Torino), Italy
- Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (Torino), Italy
| | - Chiara Enrico Bena
- IIGM—Italian Institute for Genomic Medicine, c/o IRCCS, 10060 Candiolo (Torino), Italy
- Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (Torino), Italy
| | - Silvia Grigolon
- The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
| | - Carla Bosia
- IIGM—Italian Institute for Genomic Medicine, c/o IRCCS, 10060 Candiolo (Torino), Italy
- Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy
| |
Collapse
|
|
11
|
Balasubramanian S, Raghunath A, Perumal E. Role of epigenetics in zebrafish development. Gene 2019; 718:144049. [DOI: 10.1016/j.gene.2019.144049] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 08/13/2019] [Accepted: 08/14/2019] [Indexed: 02/07/2023]
|
|
12
|
Xue S, Zhu W, Liu D, Su Z, Zhang L, Chang Q, Li P. Circulating miR-26a-1, miR-146a and miR-199a-1 are potential candidate biomarkers for acute myocardial infarction. Mol Med 2019; 25:18. [PMID: 31092195 PMCID: PMC6521554 DOI: 10.1186/s10020-019-0086-1] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Accepted: 04/22/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Acute myocardial infarction (AMI) was considered to be one of the major causes of morbidity and mortality worldwide. In order to manage the acute myocardial infarction outbreaks, accurate biomarkers for risk prediction are needed. Circulating microRNAs (miRNAs) may act as diagnostic and prognostic biomarkers for cardiovascular events. METHODS This study aimed to determine the possibility of circulating miRNAs used as biomarkers for AMI and their dynamic expression levels before and after percutaneous coronary intervention (PCI) in patients. Circulating miR-26a-1, miR-27a, miR-30d, miR-146a, miR-199a-1 and miR-423 were selected and validated in 31 AMI patients and 27 matched controls by quantitative real-time PCR (qPCR). RESULTS The expression levels of plasma miR-26a-1, miR-146a and miR-199a-1 were significantly increased in AMI patients. Receiver operating characteristic (ROC) analysis indicated that miR-26a-1, miR-146a and miR-199a-1 showed considerable diagnostic efficiency for predicting AMI. Furthermore, we demonstrated that the combination of miR-26a-1, miR-146a and miR-199a-1 facilitated AMI diagnosis. CONCLUSIONS Our findings suggest that circulating miR-26a-1, miR-146a and miR-199a-1 have the potential to be used as biomarkers for AMI diagnosis.
Collapse
Affiliation(s)
- Sheng Xue
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021 China
| | - Wenjie Zhu
- Affiliated Hospital of Qingdao University. Qingdao University, Qingdao, 266003 China
| | - Dacheng Liu
- Affiliated Hospital of Qingdao University. Qingdao University, Qingdao, 266003 China
| | - Zhe Su
- Affiliated Hospital of Qingdao University. Qingdao University, Qingdao, 266003 China
| | - Liwei Zhang
- Affiliated Hospital of Qingdao University. Qingdao University, Qingdao, 266003 China
| | - Qing Chang
- Affiliated Hospital of Qingdao University. Qingdao University, Qingdao, 266003 China
| | - Peifeng Li
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021 China
| |
Collapse
|
|
13
|
Steiman-Shimony A, Shtrikman O, Margalit H. Assessing the functional association of intronic miRNAs with their host genes. RNA (NEW YORK, N.Y.) 2018; 24:991-1004. [PMID: 29752351 PMCID: PMC6049507 DOI: 10.1261/rna.064386.117] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Accepted: 04/26/2018] [Indexed: 05/07/2023]
Abstract
In human, nearly half of the known microRNAs (miRNAs) are encoded within the introns of protein-coding genes. The embedment of these miRNA genes within the sequences of protein-coding genes alludes to a possible functional relationship between intronic miRNAs and their hosting genes. Several studies, using predicted targets, suggested that intronic miRNAs influence their hosts' function either antagonistically or synergistically. New experimental data of miRNA expression patterns and targets enable exploring this putative association by relying on actual data rather than on predictions. Here, our analysis based on currently available experimental data implies that the potential functional association between intronic miRNAs and their hosting genes is limited. For host-miRNA examples where functional associations were detected, it was manifested by either autoregulation, common targets of the miRNA and hosting gene, or through the targeting of transcripts participating in pathways in which the host gene is involved. This low prevalence of functional association is consistent with our observation that many intronic miRNAs have independent transcription start sites and are not coexpressed with the hosting gene. Yet, the intronic miRNAs that do show functional association with their hosts were found to be more evolutionarily conserved compared to other intronic miRNAs. This might suggest a selective pressure to maintain this architecture when it has a functional consequence.
Collapse
Affiliation(s)
- Avital Steiman-Shimony
- Department of Microbiology and Molecular Genetics, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel
| | - Orr Shtrikman
- Department of Microbiology and Molecular Genetics, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel
| | - Hanah Margalit
- Department of Microbiology and Molecular Genetics, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel
| |
Collapse
|
|
14
|
Zhang H, Zhang L, Sun T. Cohesive Regulation of Neural Progenitor Development by microRNA miR-26, Its Host Gene Ctdsp and Target Gene Emx2 in the Mouse Embryonic Cerebral Cortex. Front Mol Neurosci 2018. [PMID: 29515367 PMCID: PMC5825903 DOI: 10.3389/fnmol.2018.00044] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Proper proliferation and differentiation of neural progenitors (NPs) in the developing cerebral cortex are critical for normal brain formation and function. Emerging evidence has shown the importance of microRNAs (miRNAs) in regulating cortical development and the etiology of neurological disorders. Here we show that miR-26 is co-expressed with its host gene Ctdsp in the mouse embryonic cortex. We demonstrate that similar to its host gene Ctdsp2, miR-26 positively regulates proliferation of NPs through controlling the cell-cycle progression, by using miR-26 overexpression and sponge approaches. On the contrary, miR-26 target gene Emx2 limits expansion of cortical NPs, and promotes transcription of miR-26 host gene Ctdsp. Our study suggests that miR-26, its target Emx2 and its host gene Ctdsp cohesively regulate proliferation of NPs during the mouse cortical development.
Collapse
Affiliation(s)
- Haijun Zhang
- Department of Cell and Developmental Biology, Weill Cornell Medical College, Cornell University, New York, NY, United States.,Department of Genetic Medicine, Weill Cornell Medical College, Cornell University, New York, NY, United States
| | - Longbin Zhang
- Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen, China
| | - Tao Sun
- Department of Cell and Developmental Biology, Weill Cornell Medical College, Cornell University, New York, NY, United States.,Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen, China
| |
Collapse
|
|
15
|
Russo D, Della Ragione F, Rizzo R, Sugiyama E, Scalabrì F, Hori K, Capasso S, Sticco L, Fioriniello S, De Gregorio R, Granata I, Guarracino MR, Maglione V, Johannes L, Bellenchi GC, Hoshino M, Setou M, D'Esposito M, Luini A, D'Angelo G. Glycosphingolipid metabolic reprogramming drives neural differentiation. EMBO J 2017; 37:embj.201797674. [PMID: 29282205 DOI: 10.15252/embj.201797674] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Revised: 11/17/2017] [Accepted: 11/24/2017] [Indexed: 01/13/2023] Open
Abstract
Neural development is accomplished by differentiation events leading to metabolic reprogramming. Glycosphingolipid metabolism is reprogrammed during neural development with a switch from globo- to ganglio-series glycosphingolipid production. Failure to execute this glycosphingolipid switch leads to neurodevelopmental disorders in humans, indicating that glycosphingolipids are key players in this process. Nevertheless, both the molecular mechanisms that control the glycosphingolipid switch and its function in neurodevelopment are poorly understood. Here, we describe a self-contained circuit that controls glycosphingolipid reprogramming and neural differentiation. We find that globo-series glycosphingolipids repress the epigenetic regulator of neuronal gene expression AUTS2. AUTS2 in turn binds and activates the promoter of the first and rate-limiting ganglioside-producing enzyme GM3 synthase, thus fostering the synthesis of gangliosides. By this mechanism, the globo-AUTS2 axis controls glycosphingolipid reprogramming and neural gene expression during neural differentiation, which involves this circuit in neurodevelopment and its defects in neuropathology.
Collapse
Affiliation(s)
- Domenico Russo
- Institute of Protein Biochemistry, National Research Council, Naples, Italy
| | - Floriana Della Ragione
- Institute of Genetics and Biophysics, National Research Council, Naples, Italy.,IRCCS INM, Neuromed, Pozzilli, Italy
| | - Riccardo Rizzo
- Institute of Protein Biochemistry, National Research Council, Naples, Italy
| | - Eiji Sugiyama
- International Mass Imaging Center, Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan
| | - Francesco Scalabrì
- Institute of Genetics and Biophysics, National Research Council, Naples, Italy.,IRCCS INM, Neuromed, Pozzilli, Italy
| | - Kei Hori
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan
| | - Serena Capasso
- Institute of Protein Biochemistry, National Research Council, Naples, Italy.,Istituto di Ricovero e Cura a Carattere Scientifico-SDN, Naples, Italy
| | - Lucia Sticco
- Institute of Protein Biochemistry, National Research Council, Naples, Italy
| | | | - Roberto De Gregorio
- Institute of Genetics and Biophysics, National Research Council, Naples, Italy
| | - Ilaria Granata
- High Performance Computing and Networking Institute, National Research Council, Naples, Italy
| | - Mario R Guarracino
- High Performance Computing and Networking Institute, National Research Council, Naples, Italy
| | | | - Ludger Johannes
- Chemical Biology of Membranes and Therapeutic Delivery Unit, Institut Curie, INSERM U 1143, CNRS, UMR 3666, PSL Research University, Paris Cedex 05, France
| | | | - Mikio Hoshino
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan
| | - Mitsutoshi Setou
- International Mass Imaging Center, Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan
| | - Maurizio D'Esposito
- Institute of Genetics and Biophysics, National Research Council, Naples, Italy.,IRCCS INM, Neuromed, Pozzilli, Italy
| | - Alberto Luini
- Institute of Protein Biochemistry, National Research Council, Naples, Italy.,Istituto di Ricovero e Cura a Carattere Scientifico-SDN, Naples, Italy
| | - Giovanni D'Angelo
- Institute of Protein Biochemistry, National Research Council, Naples, Italy .,Istituto di Ricovero e Cura a Carattere Scientifico-SDN, Naples, Italy
| |
Collapse
|
|
16
|
D'Adamo S, Cetrullo S, Minguzzi M, Silvestri Y, Borzì RM, Flamigni F. MicroRNAs and Autophagy: Fine Players in the Control of Chondrocyte Homeostatic Activities in Osteoarthritis. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2017; 2017:3720128. [PMID: 28713485 PMCID: PMC5497632 DOI: 10.1155/2017/3720128] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Revised: 05/12/2017] [Accepted: 05/22/2017] [Indexed: 12/17/2022]
Abstract
Osteoarthritis (OA) is a debilitating degenerative disease of the articular cartilage with a multifactorial etiology. Aging, the main risk factor for OA development, is associated with a systemic oxidative and inflammatory phenotype. Autophagy is a central housekeeping system that plays an antiaging role by supporting the clearance of senescence-associated alterations of macromolecules and organelles. Autophagy deficiency has been related to OA pathogenesis because of the accumulation of cellular defects in chondrocytes. Microribonucleic acids (microRNAs or miRs) are a well-established class of posttranscriptional modulators belonging to the family of noncoding RNAs that have been identified as key players in the regulation of cellular processes, such as autophagy, by targeting their own cognate mRNAs. Here, we present a state-of-the-art literature review on the role of miRs and autophagy in the scenario of OA pathogenesis. In addition, a comprehensive survey has been performed on the functional connections of the miR network and the autophagy pathway in OA by using "microRNA," "autophagy," and "osteoarthritis" as key words. Discussion of available evidence sheds light on some aspects that need further investigation in order to reach a more comprehensive view of the potential of this topic in OA.
Collapse
Affiliation(s)
- Stefania D'Adamo
- Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy
| | - Silvia Cetrullo
- Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy
| | - Manuela Minguzzi
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
- Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Ylenia Silvestri
- Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy
| | - Rosa Maria Borzì
- Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Flavio Flamigni
- Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy
| |
Collapse
|
|
17
|
Lafourcade C, Ramírez JP, Luarte A, Fernández A, Wyneken U. MiRNAs in Astrocyte-Derived Exosomes as Possible Mediators of Neuronal Plasticity. J Exp Neurosci 2016; 10:1-9. [PMID: 27547038 PMCID: PMC4978198 DOI: 10.4137/jen.s39916] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Revised: 07/07/2016] [Accepted: 07/09/2016] [Indexed: 12/21/2022] Open
Abstract
Astrocytes use gliotransmitters to modulate neuronal function and plasticity. However, the role of small extracellular vesicles, called exosomes, in astrocyte-to-neuron signaling is mostly unknown. Exosomes originate in multivesicular bodies of parent cells and are secreted by fusion of the multivesicular body limiting membrane with the plasma membrane. Their molecular cargo, consisting of RNA species, proteins, and lipids, is in part cell type and cell state specific. Among the RNA species transported by exosomes, microRNAs (miRNAs) are able to modify gene expression in recipient cells. Several miRNAs present in astrocytes are regulated under pathological conditions, and this may have far-reaching consequences if they are loaded in exosomes. We propose that astrocyte-derived miRNA-loaded exosomes, such as miR-26a, are dysregulated in several central nervous system diseases; thus potentially controlling neuronal morphology and synaptic transmission through validated and predicted targets. Unraveling the contribution of this new signaling mechanism to the maintenance and plasticity of neuronal networks will impact our understanding on the physiology and pathophysiology of the central nervous system.
Collapse
Affiliation(s)
- Carlos Lafourcade
- Centro de Investigaciones Biomédicas, Facultad de Medicina, Universidad de los Andes, Chile
| | - Juan Pablo Ramírez
- Centro de Investigaciones Biomédicas, Facultad de Medicina, Universidad de los Andes, Chile
| | - Alejandro Luarte
- Centro de Investigaciones Biomédicas, Facultad de Medicina, Universidad de los Andes, Chile
| | - Anllely Fernández
- Centro de Investigaciones Biomédicas, Facultad de Medicina, Universidad de los Andes, Chile
| | - Ursula Wyneken
- Centro de Investigaciones Biomédicas, Facultad de Medicina, Universidad de los Andes, Chile
| |
Collapse
|
|
18
|
Wang Y, Sun B, Zhao X, Zhao N, Sun R, Zhu D, Zhang Y, Li Y, Gu Q, Dong X, Wang M, An J. Twist1-related miR-26b-5p suppresses epithelial-mesenchymal transition, migration and invasion by targeting SMAD1 in hepatocellular carcinoma. Oncotarget 2016; 7:24383-401. [PMID: 27027434 PMCID: PMC5029709 DOI: 10.18632/oncotarget.8328] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Accepted: 03/04/2016] [Indexed: 01/05/2023] Open
Abstract
UNLABELLED Twist1 is well known to induce epithelial-mesenchymal transition (EMT) and promote tumor metastasis. MicroRNAs (miRNAs) are involved in the EMT process and are associated with metastasis in hepatocellular carcinoma (HCC). In the present study, microRNA-26b-5p (miR-26b-5p) expression was consistently and significantly downregulated in HepG2-Twist1 HCC cell lines compared with HepG2-vector cell lines using microarrays (the HepG2-Twist1 cell line can stably express Twist1). miR-26b- 5p downregulation was directly mediated by Twist1 through binding to the promoter region of miR-26b-5p in HepG2-Twist1 cells by ChIP-seq technology. Both gain- and loss-of-function studies showed that miR-26b-5p dramatically suppressed EMT and the invasion ability of HCC cells in vitro. Using mouse models, tumors derived from miR- 26b-5p-overexpressed HCC cells exhibited a significant reduction in tumorigenicity compared with the control group. Subsequent investigation revealed that miR-26b-5p directly inhibited SMAD family member 1 (SMAD1) expression. miR-26b-5p repressed BMP4/Smad1 signaling following SMAD1 inhibition. Overexpression of SMAD1 reversed the function of miR-26b-5p. In human HCC tissues and mouse xenograft tumors, miR-26b-5p levels were inversely correlated with SMAD1 expression as well as metastasis. CONCLUSION miR-26b-5p suppresses Twist1-induced EMT, invasion, and metastasis of HCC cells by targeting SMAD1 and BMP4/Smad1 signaling. This suggests a promising application for miR-26b-5p in anti-HCC therapy.
Collapse
Affiliation(s)
- Yong Wang
- Department of Pathology, Tianjin Medical University, Tianjin 300070, China
| | - Baocun Sun
- Department of Pathology, Tianjin Medical University, Tianjin 300070, China
- Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin 300060, China
- Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China
| | - Xiulan Zhao
- Department of Pathology, Tianjin Medical University, Tianjin 300070, China
- Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China
| | - Nan Zhao
- Department of Pathology, Tianjin Medical University, Tianjin 300070, China
| | - Ran Sun
- Department of Pathology, Tianjin Medical University, Tianjin 300070, China
| | - Dongwang Zhu
- Department of Prosthodontics, Affiliated Stomatological Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Yanhui Zhang
- Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin 300060, China
| | - Yanlei Li
- Department of Pathology, Tianjin Medical University, Tianjin 300070, China
| | - Qiang Gu
- Department of Pathology, Tianjin Medical University, Tianjin 300070, China
- Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China
| | - Xueyi Dong
- Department of Pathology, Tianjin Medical University, Tianjin 300070, China
- Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China
| | - Meili Wang
- Department of Pathology, Tianjin Medical University, Tianjin 300070, China
| | - Jindan An
- Department of Pathology, Mudanjiang Medical University, Heilongjiang 157011, China
| |
Collapse
|
|
19
|
Jiang LP, Zhu ZT, He CY. Expression of miRNA-26b in the diagnosis and prognosis of patients with non-small-cell lung cancer. Future Oncol 2016; 12:1105-15. [PMID: 27033050 DOI: 10.2217/fon.16.21] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVE To investigate the correlation between miR-26b and non-small-cell lung cancer (NSCLC). MATERIALS & METHODS NSCLC tissues and normal lung tissues that were more than 7 cm adjacent from tumor were collected from 154 NSCLC patients. Additionally, 63 normal specimens from benign lung disease were selected as the control group. Real-time fluorescent quantitative PCR was used to detect miR-26b expression in tissues. RESULT miR-26b expression in NSCLC tissues was significantly lower than in other two types of tissues. Receiver operating characteristic curve analysis showed that the area under the curve was 0.856 with sensitivity and specificity of 79.9 and 79.4%, respectively. miR-26b expression was a risk factor for poor prognosis of NSCLC. CONCLUSION The expression of miR-26b is downregulated in NSCLC tissues, and it might be useful in the diagnosis and prognosis of NSCLC patients.
Collapse
Affiliation(s)
- Li-Peng Jiang
- Department of Radiation Oncology, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, PR China
| | - Zhi-Tu Zhu
- Department of Oncology, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, PR China
| | - Chun-Yan He
- Department of Prosthodontics, Second Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, PR China
| |
Collapse
|
|
20
|
Chen CYA, Chang JT, Ho YF, Shyu AB. MiR-26 down-regulates TNF-α/NF-κB signalling and IL-6 expression by silencing HMGA1 and MALT1. Nucleic Acids Res 2016; 44:3772-87. [PMID: 27025651 PMCID: PMC4856999 DOI: 10.1093/nar/gkw205] [Citation(s) in RCA: 85] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 03/18/2016] [Indexed: 01/14/2023] Open
Abstract
MiR-26 has emerged as a key tumour suppressor in various cancers. Accumulating evidence supports that miR-26 regulates inflammation and tumourigenicity largely through down-regulating IL-6 production, but the underlying mechanism remains obscure. Here, combining a transcriptome-wide approach with manipulation of cellular miR-26 levels, we showed that instead of directly targeting IL-6 mRNA for gene silencing, miR-26 diminishes IL-6 transcription activated by TNF-α through silencing NF-κB signalling related factors HMGA1 and MALT1. We demonstrated that miR-26 extensively dampens the induction of many inflammation-related cytokine, chemokine and tissue-remodelling genes that are activated via NF-κB signalling pathway. Knocking down both HMGA1 and MALT1 by RNAi had a silencing effect on NF-κB-responsive genes similar to that caused by miR-26. Moreover, we discovered that poor patient prognosis in human lung adenocarcinoma is associated with low miR-26 and high HMGA1 or MALT1 levels and not with levels of any of them individually. These new findings not only unravel a novel mechanism by which miR-26 dampens IL-6 production transcriptionally but also demonstrate a direct role of miR-26 in down-regulating NF-κB signalling pathway, thereby revealing a more critical and broader role of miR-26 in inflammation and cancer than previously realized.
Collapse
Affiliation(s)
- Chyi-Ying A Chen
- Department of Biochemistry and Molecular Biology, McGovern Medical School, Houston, TX 77030, USA
| | - Jeffrey T Chang
- Department of Integrative Biology and Pharmacology, McGovern Medical School, Houston, TX 77030, USA School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Yi-Fang Ho
- Department of Biochemistry and Molecular Biology, McGovern Medical School, Houston, TX 77030, USA
| | - Ann-Bin Shyu
- Department of Biochemistry and Molecular Biology, McGovern Medical School, Houston, TX 77030, USA
| |
Collapse
|
|
21
|
Wang G, Sun Y, He Y, Ji C, Hu B, Sun Y. miR-26a promoted by interferon-alpha inhibits hepatocellular carcinoma proliferation and migration by blocking EZH2. Genet Test Mol Biomarkers 2015; 19:30-6. [PMID: 25494962 DOI: 10.1089/gtmb.2014.0245] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUNDS Interferon (IFN)-α has been used to treat hepatocellular carcinoma (HCC). Here, we report that the IFN-α-induced microRNA-26a (miR-26a) can inhibit HCC proliferation and invasion by suppressing enhancer of zeste homologue 2 (EZH2) expression in tumor cells. MATERIALS AND METHODS First, the miR-26a transcription level was quantified by real-time quantitative PCR in the HCC specimens from IFN-α-treated HCC patients. Next, we transfected HepG2 cells with miR-26a mimics and miR control, and then we investigated the influence of miR-26a mimic transfection on HepG2 cell proliferation and invasion. RESULTS It was shown that there was increased miR-26a accompanied with downregulated EZH2 expression in the HCC specimens, and EZH2 mRNA levels were inversely correlated with miR-26a expression. There was a dose-response correlation between the IFN-α dosage and EZH2 expression. In addition, the miR-26a mimic transfection decreased the EZH2 expression level significantly in the transfected HepG2 cells and inhibited HepG2 cell proliferation and invasion effectively. CONCLUSION Our results indicate that miR-26a exerts growth inhibition in HCC and that its inhibitory effect is mediated briefly by blocking EZH2 expression.
Collapse
Affiliation(s)
- Gang Wang
- 1 Department of Oncology, Jinan Central Hospital, Shandong University , Jinan, People's Republic of China
| | | | | | | | | | | |
Collapse
|
|
22
|
ErbB2-intronic microRNA-4728: a novel tumor suppressor and antagonist of oncogenic MAPK signaling. Cell Death Dis 2015; 6:e1742. [PMID: 25950472 PMCID: PMC4669696 DOI: 10.1038/cddis.2015.116] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Revised: 03/10/2015] [Accepted: 03/23/2015] [Indexed: 12/22/2022]
Abstract
Although the role of the ErbB2/HER2 oncogene in cancers has been extensively studied, how ErbB2 is regulated remains poorly understood. A novel microRNA, mir-4728, was recently found within an intron of the ErbB2 gene. However, the function and clinical relevance of this intronic miRNA are completely unknown. Here, we demonstrate that mir-4728 is a negative regulator of MAPK signaling through directly targeting the ERK upstream kinase MST4 and exerts numerous tumor-suppressive properties in vitro and in animal models. Importantly, our patient sample study shows that mir-4728 was under-expressed in breast tumors compared with normal tissue, and loss of mir-4728 correlated with worse overall patient survival. These results strongly suggest that mir-4728 is a tumor-suppressive miRNA that controls MAPK signaling through targeting MST4, revealing mir-4728's significance as a potential prognostic factor and target for therapeutic intervention in cancer. Moreover, this study represents a conceptual advance by providing strong evidence that a tumor-suppressive miRNA can antagonize the canonical signaling of its host oncogene.
Collapse
|
|
23
|
Mammalian introns: when the junk generates molecular diversity. Int J Mol Sci 2015; 16:4429-52. [PMID: 25710723 PMCID: PMC4394429 DOI: 10.3390/ijms16034429] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Revised: 02/06/2015] [Accepted: 02/11/2015] [Indexed: 01/14/2023] Open
Abstract
Introns represent almost half of the human genome, yet their vast majority is eliminated from eukaryotic transcripts through RNA splicing. Nevertheless, they feature key elements and functions that deserve further interest. At the level of DNA, introns are genomic segments that can shelter independent transcription units for coding and non-coding RNAs which transcription may interfere with that of the host gene, and regulatory elements that can influence gene expression and splicing itself. From the RNA perspective, some introns can be subjected to alternative splicing. Intron retention appear to provide some plasticity to the nature of the protein produced, its distribution in a given cell type and timing of its translation. Intron retention may also serve as a switch to produce coding or non-coding RNAs from the same transcription unit. Conversely, splicing of introns has been directly implicated in the production of small regulatory RNAs. Hence, splicing of introns also appears to provide plasticity to the type of RNA produced from a genetic locus (coding, non-coding, short or long). We addressed these aspects to add to our understanding of mechanisms that control the fate of introns and could be instrumental in regulating genomic output and hence cell fate.
Collapse
|
|
24
|
Yao L, Han C, Song K, Zhang J, Lim K, Wu T. Omega-3 Polyunsaturated Fatty Acids Upregulate 15-PGDH Expression in Cholangiocarcinoma Cells by Inhibiting miR-26a/b Expression. Cancer Res 2015; 75:1388-98. [PMID: 25691459 DOI: 10.1158/0008-5472.can-14-2561] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Accepted: 01/26/2015] [Indexed: 12/19/2022]
Abstract
Prostaglandin E2 (PGE2) is a proinflammatory lipid mediator that promotes cancer growth. The 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes oxidation of the 15(S)-hydroxyl group of PGE2, leading to its inactivation. Therefore, 15-PGDH induction may offer a strategy to treat cancers that are driven by PGE2, such as human cholangiocarcinoma. Here, we report that omega-3 polyunsaturated fatty acids (ω-3 PUFA) upregulate 15-PGDH expression by inhibiting miR-26a and miR-26b, thereby contributing to ω-3 PUFA-induced inhibition of human cholangiocarcinoma cell growth. Treatment of human cholangiocarcinoma cells (CCLP1 and TFK-1) with ω-3 PUFA (DHA) or transfection of these cells with the Fat-1 gene (encoding Caenorhabditis elegans desaturase, which converts ω-6 PUFA to ω-3 PUFA) significantly increased 15-PGDH enzymes levels, but with little effect on the activity of the 15-PGDH gene promoter. Mechanistic investigations revealed that this increase in 15-PGDH levels in cells was mediated by a reduction in the expression of miR-26a and miR-26b, which target 15-PGDH mRNA and inhibit 15-PGDH translation. These findings were extended by the demonstration that overexpressing miR-26a or miR-26b decreased 15-PGDH protein levels, reversed ω-3 PUFA-induced accumulation of 15-PGDH protein, and prevented ω-3 PUFA-induced inhibition of cholangiocarcinoma cell growth. We further observed that ω-3 PUFA suppressed miR-26a and miR-26b by inhibiting c-myc, a transcription factor that regulates miR-26a/b. Accordingly, c-myc overexpression enhanced expression of miR-26a/b and ablated the ability of ω-3 PUFA to inhibit cell growth. Taken together, our results reveal a novel mechanism for ω-3 PUFA-induced expression of 15-PGDH in human cholangiocarcinoma and provide a preclinical rationale for the evaluation of ω-3 PUFA in treatment of this malignancy.
Collapse
Affiliation(s)
- Lu Yao
- Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana
| | - Chang Han
- Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana
| | - Kyoungsub Song
- Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana
| | - Jinqiang Zhang
- Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana
| | - Kyu Lim
- Department of Biochemistry, College of Medicine, Cancer Research Institute and Infection Signaling, Network Research Center, Chungnam National University, Daejeon, Korea
| | - Tong Wu
- Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
| |
Collapse
|
|
25
|
Abstract
MicroRNAs (miRNAs) are transcriptional and posttranscriptional regulators involved in nearly all known biological processes in distant eukaryotic clades. Their discovery and functional characterization have broadened our understanding of biological regulatory mechanisms in animals and plants. They show both evolutionary conserved and unique features across Metazoa. Here, we present the current status of the knowledge about the role of miRNA in development, growth, and physiology of teleost fishes, in comparison to other vertebrates. Infraclass Teleostei is the most abundant group among vertebrate lineage. Fish are an important component of aquatic ecosystems and human life, being the prolific source of animal proteins worldwide and a vertebrate model for biomedical research. We review miRNA biogenesis, regulation, modifications, and mechanisms of action. Specific sections are devoted to the role of miRNA in teleost development, organogenesis, tissue differentiation, growth, regeneration, reproduction, endocrine system, and responses to environmental stimuli. Each section discusses gaps in the current knowledge and pinpoints the future directions of research on miRNA in teleosts.
Collapse
Affiliation(s)
| | - Igor Babiak
- Faculty of Aquaculture and Biosciences, University of Nordland, Bodø, Norway
| |
Collapse
|
|
26
|
Choi E, Choi E, Hwang KC. MicroRNAs as novel regulators of stem cell fate. World J Stem Cells 2013; 5:172-187. [PMID: 24179605 PMCID: PMC3812521 DOI: 10.4252/wjsc.v5.i4.172] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2013] [Revised: 07/13/2013] [Accepted: 08/17/2013] [Indexed: 02/06/2023] Open
Abstract
Mounting evidence in stem cell biology has shown that microRNAs (miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineage-specific differentiation, and somatic cell reprogramming. These functions are tightly regulated by specific gene expression patterns that involve miRNAs and transcription factors. To maintain stem cell pluripotency, specific miRNAs suppress transcription factors that promote differentiation, whereas to initiate differentiation, lineage-specific miRNAs are upregulated via the inhibition of transcription factors that promote self-renewal. Small molecules can be used in a similar manner as natural miRNAs, and a number of natural and synthetic small molecules have been isolated and developed to regulate stem cell fate. Using miRNAs as novel regulators of stem cell fate will provide insight into stem cell biology and aid in understanding the molecular mechanisms and crosstalk between miRNAs and stem cells. Ultimately, advances in the regulation of stem cell fate will contribute to the development of effective medical therapies for tissue repair and regeneration. This review summarizes the current insights into stem cell fate determination by miRNAs with a focus on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.
Collapse
|
|
27
|
Bian S, Xu TL, Sun T. Tuning the cell fate of neurons and glia by microRNAs. Curr Opin Neurobiol 2013; 23:928-34. [PMID: 23978589 DOI: 10.1016/j.conb.2013.08.002] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2013] [Revised: 08/02/2013] [Accepted: 08/05/2013] [Indexed: 12/22/2022]
Abstract
The proper function of the nervous system depends on precise production and connection of distinct neurons and glia. Cell fate determination of neurons and glia is tightly controlled by complex gene expression regulation in the developing and adult nervous system. Emerging evidence has demonstrated the importance of noncoding microRNAs (miRNAs) in neural development and function. This review highlights current discoveries of miRNA functions in specifying neuronal and glial cell fate. We summarize the roles of miRNAs in expansion and differentiation of neural stem cells, specification of neuronal subtypes and glial cells, reprogramming of functional neurons from embryonic stem cells and fibroblasts, and left-right asymmetric organization of neuronal subtypes. Investigating the network of interactions between miRNAs and target genes will reveal new gene regulation machinery involved in tuning the cell fate decisions of neurons and glia.
Collapse
Affiliation(s)
- Shan Bian
- Department of Cell and Developmental Biology, Cornell University Weill Medical College, 1300 York Avenue, Box 60, New York, NY 10065, United States
| | | | | |
Collapse
|
|
28
|
Ji F, Lv X, Jiao J. The role of microRNAs in neural stem cells and neurogenesis. J Genet Genomics 2013; 40:61-6. [PMID: 23439404 DOI: 10.1016/j.jgg.2012.12.008] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2012] [Revised: 12/24/2012] [Accepted: 12/27/2012] [Indexed: 12/30/2022]
Abstract
Neural stem cells give rise to neurons through the process of neurogenesis, which includes neural stem cell proliferation, fate determination of new neurons, as well as the new neuron's migration, maturation and integration. Currently, neurogenesis is divided into two phases: embryonic and adult phases. Embryonic neurogenesis occurs at high levels to form the central nervous system. Adult neurogenesis has been consistently identified only in restricted regions and occurs at low levels. As the basic process for embryonic neurodevelopment and adult brain maintenance, neurogenesis is tightly regulated by many factors and pathways. MicroRNA, short non-coding RNA that regulates gene expression at the post-transcriptional level, appears to be involved in multiple steps of neurogenesis. This review summarizes the emerging role of microRNAs in regulating embryonic and adult neurogenesis, with a particular emphasis on the proliferation and differentiation of neural stem cells.
Collapse
Affiliation(s)
- Fen Ji
- Institute of Zoology, State Key Laboratory of Reproductive Biology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101, China
| | | | | |
Collapse
|
|
29
|
Gao X, Qiao Y, Han D, Zhang Y, Ma N. Enemy or partner: relationship between intronic micrornas and their host genes. IUBMB Life 2012; 64:835-40. [PMID: 22941954 DOI: 10.1002/iub.1079] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2012] [Accepted: 07/19/2012] [Indexed: 02/03/2023]
Abstract
In the past several years, microRNAs have been identified as a class of important regulators of gene expression. One hot topic in the microRNA field is the location of microRNA genes. Most microRNAs are called intronic microRNAs, which are encoded in the introns of coding or non-coding genes. Some research studies have shown that intronic miRNAs coexpress and act similarly to their host genes; however, other research studies have suggested that their level of expression and function are opposite to that of their host genes. Intronic microRNAs have been reported to play an antagonistic or synergetic role as an enemy or a partner of their host genes. Elucidation of the relationship between intronic microRNAs and their host genes will facilitate a deeper understanding of gene expression and the function of introns. This mini review will discuss recent research addressing intronic microRNAs and their host genes.
Collapse
Affiliation(s)
- Xu Gao
- Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
| | | | | | | | | |
Collapse
|
|
30
|
Chan AWS, Kocerha J. The Path to microRNA Therapeutics in Psychiatric and Neurodegenerative Disorders. Front Genet 2012; 3:82. [PMID: 22629284 PMCID: PMC3354561 DOI: 10.3389/fgene.2012.00082] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Accepted: 04/26/2012] [Indexed: 01/08/2023] Open
Abstract
The microRNA (miRNA) class of non-coding RNAs exhibit a diverse range of regulatory roles in neuronal functions that are conserved from lower vertebrates to primates. Disruption of miRNA expression has compellingly been linked to pathogenesis in neuropsychiatric and neurodegenerative disorders, such as schizophrenia, Alzheimer’s disease, and autism. The list of transcript targets governed by a single miRNA provide a molecular paradigm applicable for therapeutic intervention. Indeed, reports have shown that specific manipulation of a miRNA in cell or animal models can significantly alter phenotypes linked with neurological disease. Here, we review how a diverse range of biological systems, including Drosophila, rodents, and primates such as monkeys and humans, can be integrated into the translation of miRNAs as novel clinical targets.
Collapse
|