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Shamsad A, Gautam T, Singh R, Banerjee M. Genetic and epigenetic alterations associated with gestational diabetes mellitus and adverse neonatal outcomes. World J Clin Pediatr 2025; 14:99231. [DOI: 10.5409/wjcp.v14.i1.99231] [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: 07/17/2024] [Revised: 10/03/2024] [Accepted: 10/31/2024] [Indexed: 12/20/2024] Open
Abstract
Gestational diabetes mellitus (GDM) is a metabolic disorder, recognised during 24-28 weeks of pregnancy. GDM is linked with adverse newborn outcomes such as macrosomia, premature delivery, metabolic disorder, cardiovascular, and neurological disorders. Recent investigations have focused on the correlation of genetic factors such as β-cell function and insulin secretary genes (transcription factor 7 like 2, potassium voltage-gated channel subfamily q member 1, adiponectin etc.) on maternal metabolism during gestation leading to GDM. Epigenetic alterations like DNA methylation, histone modification, and miRNA expression can influence gene expression and play a dominant role in feto-maternal metabolic pathways. Interactions between genes and environment, resulting in differential gene expression patterns may lead to GDM. Researchers suggested that GDM women are more susceptible to insulin resistance, which alters intrauterine surroundings, resulting hyperglycemia and hyperinsulinemia. Epigenetic modifications in genes affecting neuroendocrine activities, and metabolism, increase the risk of obesity and type 2 diabetes in offspring. There is currently no treatment or effective preventive method for GDM, since the molecular processes of insulin resistance are not well understood. The present review was undertaken to understand the pathophysiology of GDM and its effects on adverse neonatal outcomes. In addition, the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.
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Affiliation(s)
- Amreen Shamsad
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
| | - Tanu Gautam
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
| | - Renu Singh
- Department of Obstetrics and Gynecology, King George’s Medical University, Lucknow 226003, Uttar Pradesh, India
| | - Monisha Banerjee
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
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2
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Peluzzo TM, Vieira AS, Matos AHB, Silveira C, Martin M, Filho ORC, Rezende TJR, Martinez ARM, França MC. Plasma miRNAs Correlate with Structural Brain and Cardiac Damage in Friedreich's Ataxia. CEREBELLUM (LONDON, ENGLAND) 2024; 24:15. [PMID: 39688804 DOI: 10.1007/s12311-024-01766-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 10/23/2024] [Indexed: 12/18/2024]
Abstract
Friedreich's Ataxia (FRDA) is the most common autosomal recessive ataxia worldwide and is caused by biallelic unstable intronic GAA expansions at FXN. With its limited therapy and the recent approval of the first disease-modifying agent for FRDA, the search for biological markers is urgently needed to assist and ease the development of therapies. MiRNAs have emerged as promising biomarkers in various medical fields such as oncology, cardiology, epilepsy and neurology as well. Cell-free plasmatic miRNAs have potential advantages as biomarkers because of their size, stability against blood RNases, relative ease of obtaining, storage and measurement. In this study, we attempted to characterize the plasma miRNA signature (RNA-Seq followed by qRT-PCR) and its clinical/structural correlates in a cohort of Brazilian patients with FRDA. Our results showed that miR-26a-5p is upregulated and miR-15a-5p is downregulated. The first was correlated with age at onset, cerebellum volume, spinal cord cross-sectional area (C2-CSA) and the left ventricle mass (LV_Mass). For the miR-15a-5p, significant correlations were found with cerebellum volume, spinal cord eccentricity and LV_Mass. It has been previously hypothesized that these miRs target BDNF, modulating its expression and, when this gene is downregulated, it leads to neuronal loss, explaining the ataxic phenotype and our results reinforce this hypothesis. The miR-26a-5p was already associated with cardiomyocyte hypertrophy through the increased NLRP3 inflammasome activity, which is indirectly linked with cardiac hypertrophy. Considering that, we propose these miRNAs as possible prognostic biomarkers for FRDA. However, longitudinal studies are still needed to validate their clinical use.
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Affiliation(s)
- Thiago M Peluzzo
- Department of Translacional Medicine, School of Medical Sciences, University of Campinas - UNICAMP, Campinas, Sao Paulo, Brazil
| | - André S Vieira
- Department of Structural and Functional Biology, Institute of Biology, University of Campinas - UNICAMP, Campinas, Sao Paulo, Brazil
| | - Alexandre H B Matos
- Department of Neurology, School of Medical Sciences, University of Campinas - UNICAMP, Rua Tessália Vieira de Camargo, 126. Cidade Universitária "Zeferino Vaz" Campinas, Campinas, SP, 13083-887, Brazil
| | - Cynthia Silveira
- Department of Neurology, School of Medical Sciences, University of Campinas - UNICAMP, Rua Tessália Vieira de Camargo, 126. Cidade Universitária "Zeferino Vaz" Campinas, Campinas, SP, 13083-887, Brazil
| | - Mariana Martin
- Department of Translacional Medicine, School of Medical Sciences, University of Campinas - UNICAMP, Campinas, Sao Paulo, Brazil
| | - Otávio R C Filho
- Department of Neurology, School of Medical Sciences, University of Campinas - UNICAMP, Rua Tessália Vieira de Camargo, 126. Cidade Universitária "Zeferino Vaz" Campinas, Campinas, SP, 13083-887, Brazil
| | - Thiago J R Rezende
- Department of Neurology, School of Medical Sciences, University of Campinas - UNICAMP, Rua Tessália Vieira de Camargo, 126. Cidade Universitária "Zeferino Vaz" Campinas, Campinas, SP, 13083-887, Brazil
| | - Alberto R M Martinez
- Department of Neurology, School of Medical Sciences, University of Campinas - UNICAMP, Rua Tessália Vieira de Camargo, 126. Cidade Universitária "Zeferino Vaz" Campinas, Campinas, SP, 13083-887, Brazil
| | - Marcondes C França
- Department of Neurology, School of Medical Sciences, University of Campinas - UNICAMP, Rua Tessália Vieira de Camargo, 126. Cidade Universitária "Zeferino Vaz" Campinas, Campinas, SP, 13083-887, Brazil.
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Hemedan AA, Satagopam V, Schneider R, Ostaszewski M. Cohort-specific boolean models highlight different regulatory modules during Parkinson's disease progression. iScience 2024; 27:110956. [PMID: 39429779 PMCID: PMC11489052 DOI: 10.1016/j.isci.2024.110956] [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: 03/28/2024] [Revised: 07/02/2024] [Accepted: 09/10/2024] [Indexed: 10/22/2024] Open
Abstract
Parkinson's disease (PD) involves complex molecular interactions and diverse comorbidities. To better understand its molecular mechanisms, we employed systems medicine approaches using the PD map, a detailed repository of PD-related interactions and applied Probabilistic Boolean Networks (PBNs) to capture the stochastic nature of molecular dynamics. By integrating cohort-level and real-world patient data, we modeled PD's subtype-specific pathway deregulations, providing a refined representation of its molecular landscape. Our study identifies key regulatory biomolecules and pathways that vary across PD subtypes, offering insights into the disease's progression and patient stratification. These findings have significant implications for the development of targeted therapeutic interventions.
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Affiliation(s)
- Ahmed Abdelmonem Hemedan
- Bioinformatics Core Unit, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Venkata Satagopam
- Bioinformatics Core Unit, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Reinhard Schneider
- Bioinformatics Core Unit, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Marek Ostaszewski
- Bioinformatics Core Unit, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
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Ghaneialvar H, Mohseni MM, Kenarkoohi A, Kakaee S. Are miR-26a and miR-26b microRNAs potent prognostic markers of gestational diabetes? Health Sci Rep 2024; 7:e2152. [PMID: 38831779 PMCID: PMC11144624 DOI: 10.1002/hsr2.2152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 03/02/2024] [Accepted: 05/08/2024] [Indexed: 06/05/2024] Open
Abstract
Background Gestational diabetes mellitus is a common public health problem, accompanied by complications for the mother and fetus. So, introducing new biomarkers to identify early diabetes is essential. As serum miRNAs are potentially appropriate markers, we investigated miR-26a and miR-26b expression levels in pregnant women with and without gestational diabetes. Method Demographic and clinical characteristics of 40 gestational diabetic patients and 40 healthy controls were assessed. The expression level of miR-26a and miR-26b microRNAs was measured by real-time PCR. Statistical analysis was done with GraphPad Prism software (version 8.4.3). Result The findings of this study showed that the expression level of miR-26a and miR-26b increased in women with gestational diabetes compared with healthy pregnant women, but the increase in expression was only significant for miR-26a (p < 0.05). Conclusion According to the statistical and ROC curves, we suggest miR-26a as a potential biomarker for the early diagnosis of gestational diabetes mellitus.
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Affiliation(s)
- Hori Ghaneialvar
- Biotechnology and Medicinal Plants Research CenterIlam University of Medical SciencesIlamIran
| | | | - Azra Kenarkoohi
- Department of Laboratory Sciences, School of Allied Medical SciencesIlam University of Medical SciencesIlamIran
| | - Saeed Kakaee
- Biotechnology and Medicinal Plants Research CenterIlam University of Medical SciencesIlamIran
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Toljic M, Nikolic N, Joksic I, Carkic J, Munjas J, Karadzov Orlic N, Milasin J. Expression of miRNAs and proinflammatory cytokines in pregnant women with gestational diabetes mellitus. J Reprod Immunol 2024; 162:104211. [PMID: 38342070 DOI: 10.1016/j.jri.2024.104211] [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: 09/25/2023] [Revised: 12/22/2023] [Accepted: 01/31/2024] [Indexed: 02/13/2024]
Abstract
Altered microRNAs (miRNAs1) and cytokines expression levels are associated with several pregnancy-induced complications. We evaluated the profile of circulating miRNAs (miR-17, miR-29a and miR-181a) and proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-17) in women with gestational diabetes mellitus (GDM2), as well as their potential use as GDM biomarkers. The case-control study included 65 pregnant women divided into 2 groups - GDM and control. Expression levels of miRNAs in plasma samples and cytokines mRNA isolated from peripheral blood buffy coat were analyzed by quantitative real-time PCR (qPCR3). Significant miR-29a downregulation was found in GDM compared to the control group, and was even more significant after adjustments for covariates. miR-17 and miR-181a expression levels did not differ between the examined groups. Expression levels of IL-1β were significantly higher in GDM group compared to controls, while TNF-α, IL-6 and IL-17 did not show significant changes in expression between the two groups. As jugded from the ROC curve analysis, miR-29a and IL-1β had a significant capacity to discriminate between CG and GDM. Additionally, a positive correlation was established between IL-1β and TNF-α in the GDM group. GDM appeared to be associated with altered levels of miR-29a and IL-1β making them markers of this condition.
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Affiliation(s)
- Mina Toljic
- Genetic Laboratory Department, Obstetrics and Gynecology Clinic "Narodni Front", Kraljice Natalije Street 62, 11000 Belgrade, Serbia
| | - Nadja Nikolic
- Department of Human Genetics, School of Dental Medicine, University of Belgrade, Street Dr Subotica 8, 11000 Belgrade, Serbia
| | - Ivana Joksic
- Genetic Laboratory Department, Obstetrics and Gynecology Clinic "Narodni Front", Kraljice Natalije Street 62, 11000 Belgrade, Serbia.
| | - Jelena Carkic
- Department of Human Genetics, School of Dental Medicine, University of Belgrade, Street Dr Subotica 8, 11000 Belgrade, Serbia
| | - Jelena Munjas
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Street Vojvode Stepe 450, 11000 Belgrade, Serbia
| | - Natasa Karadzov Orlic
- High-Risk Pregnancy Department, Obstetrics and Gynecology Clinic "Narodni Front", School of Medicine, University of Belgrade, Kraljice Natalije Street 62, 11000 Belgrade, Serbia
| | - Jelena Milasin
- Department of Human Genetics, School of Dental Medicine, University of Belgrade, Street Dr Subotica 8, 11000 Belgrade, Serbia
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Kunysz M, Cieśla M, Darmochwał-Kolarz D. Evaluation of miRNA Expression in Patients with Gestational Diabetes Mellitus: Investigating Diagnostic Potential and Clinical Implications. Diabetes Metab Syndr Obes 2024; 17:881-891. [PMID: 38414865 PMCID: PMC10898488 DOI: 10.2147/dmso.s443755] [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: 11/01/2023] [Accepted: 01/24/2024] [Indexed: 02/29/2024] Open
Abstract
Purpose Gestational diabetes mellitus (GDM) is common pregnancy complication (8%), characterized by hyperglycemia resulting from pathological homeostatic mechanisms. There's a concerning trend of increasing GDM prevalence. New markers, particularly epigenetic ones, are sought for early detection and enhanced care. miRNA are small non-coding RNA molecules. The main goal was to investigate the potential role of miRNA (miR-16-5p, miR-222-3p, miR-21-5p) in GDM and their association with clinical features. Patients and Methods The study included 72 pregnant patients, with 42 having GDM and 30 in the control group. miRNA expression was measured using ELISA. Results There were no significant differences in miR-222-3p expression between GDM patients and the control group. The GDM group exhibited a positive correlation between miR-16-5p expression and miR-21-5p expression as well as between miR-16-5p expression and insulin resistance. In the GDM group, a positive correlation was observed between miR-21-5p expression and fasting glucose levels. Conclusion Results do not confirm the role of miR-222-3p in GDM pathogenesis or as a diagnostic marker. Additionally, a role for miR-16-5p in GDM pathogenesis was observed. Furthermore, a potential role for miR-21-5p in monitoring GDM treatment is indicated.
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Affiliation(s)
- Mateusz Kunysz
- Department of Obstetrics & Gynecology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow, Rzeszow, 35-959, Poland
| | - Marek Cieśla
- College of Medical Sciences, University of Rzeszow, Rzeszow, 35-959, Poland
| | - Dorota Darmochwał-Kolarz
- Department of Obstetrics & Gynecology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow, Rzeszow, 35-959, Poland
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Ustianowski Ł, Udzik J, Szostak J, Gorący A, Ustianowska K, Pawlik A. Genetic and Epigenetic Factors in Gestational Diabetes Mellitus Pathology. Int J Mol Sci 2023; 24:16619. [PMID: 38068941 PMCID: PMC10706782 DOI: 10.3390/ijms242316619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 11/14/2023] [Accepted: 11/20/2023] [Indexed: 12/18/2023] Open
Abstract
Gestational diabetes (GDM) is the carbohydrate intolerance occurring during pregnancy. The risk factors of GDM include obesity, advanced maternal age, polycystic ovary syndrome, multigravidity, a sedentary lifestyle, and pre-existing hypertension. Additionally, complex genetic and epigenetic processes are also believed to play a crucial role in the development of GDM. In this narrative review, we discuss the role of genetic and epigenetic factors in gestational diabetes mellitus pathogenesis.
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Affiliation(s)
- Łukasz Ustianowski
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (Ł.U.); (J.U.); (K.U.)
| | - Jakub Udzik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (Ł.U.); (J.U.); (K.U.)
- Department of Cardiac Surgery, Pomeranian Medical University, 70-111 Szczecin, Poland
| | - Joanna Szostak
- Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland;
| | - Anna Gorący
- Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, 70-111 Szczecin, Poland;
| | - Klaudia Ustianowska
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (Ł.U.); (J.U.); (K.U.)
| | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (Ł.U.); (J.U.); (K.U.)
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Ejaz M, Usman SM, Amir S, Khan MJ. Holistic expression of miR-17-92 cluster in obesity, kidney diseases, cardiovascular diseases, and diabetes. Mol Biol Rep 2023; 50:6913-6925. [PMID: 37329480 DOI: 10.1007/s11033-023-08549-4] [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: 04/09/2023] [Accepted: 05/24/2023] [Indexed: 06/19/2023]
Abstract
miR-17-92 cluster encodes six micro RNAs (miRNAs) and plays a crucial role in the regulation of various cellular processes. Aberrant expression of this cluster may result in the onset of several diseases. Initially, the role of miR-17-92 cluster in tumorigenesis was discovered but recent research has also uncovered its role in other diseases. Members of the cluster may serve as potential biomarkers in the prognosis, diagnosis, and treatment of several diseases and their complications. In this article, we have reviewed the recent research carried out on the expression pattern of miR-17-92 cluster in non-communicable diseases i.e., obesity, cardiovascular diseases (CVD), kidney diseases (KD) and diabetes mellitus (DM). We examined miR-17-92 role in pathological processes and their potential importance as biomarkers. Each member of the cluster miR-17-92 was upregulated in obesity. miR-18a, miR-19b-3p, miR20a, and miR92a were significantly upregulated in CVD. An equal fraction of the cluster was dysregulated (upregulated and downregulated) in diabetes; however, miR-17-92 was downregulated in most studies on CKD.
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Affiliation(s)
- Maheen Ejaz
- Department of Biosciences, COMSATS University Islamabad, Park Road, Chak Shahzad Islamabad, Islamabad, 45550, Pakistan
| | - Syed Mohammad Usman
- Department of Biochemistry, McMaster University, Hamilton, ON, L8S 4L8, Canada
| | - Saira Amir
- Department of Biosciences, COMSATS University Islamabad, Park Road, Chak Shahzad Islamabad, Islamabad, 45550, Pakistan
| | - Muhammad Jawad Khan
- Department of Biosciences, COMSATS University Islamabad, Park Road, Chak Shahzad Islamabad, Islamabad, 45550, Pakistan.
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da Silva PHCM, Santos KDF, da Silva L, da Costa CCP, Santos RDS, Reis AADS. MicroRNAs Associated with the Pathophysiological Mechanisms of Gestational Diabetes Mellitus: A Systematic Review for Building a Panel of miRNAs. J Pers Med 2023; 13:1126. [PMID: 37511739 PMCID: PMC10381583 DOI: 10.3390/jpm13071126] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 07/07/2023] [Accepted: 07/07/2023] [Indexed: 07/30/2023] Open
Abstract
miRNAs, a class of small non-coding RNAs, play a role in post-transcriptional gene expression. Therefore, this study aimed to conduct a systematic review of miRNAs associated with GDM to build a panel of miRNAs. A bibliographic search was carried out in the PubMed/Medline, Virtual Health Library (VHL), Web of Science, and EMBASE databases, selecting observational studies in English without time restriction. The protocol was registered on the PROSPERO platform (number CRD42021291791). Fifty-five studies were included in this systematic review, and 82 altered miRNAs in GDM were identified. In addition, four miRNAs were most frequently dysregulated in GDM (mir-16-5p, mir-20a-5p, mir-222-3p, and mir-330-3p). The dysregulation of these miRNAs is associated with the mechanisms of cell cycle homeostasis, growth, and proliferation of pancreatic β cells, glucose uptake and metabolism, insulin secretion, and resistance. On the other hand, identifying miRNAs associated with GDM and elucidating its main mechanisms can assist in the characterization and definition of potential biomarkers for the diagnosis and treatment of GDM.
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Affiliation(s)
- Pedro Henrique Costa Matos da Silva
- Laboratory of Molecular Pathology, Institute of Biological Sciences, Federal University of Goiás (UFG), Goiânia 74690-090, GO, Brazil (K.d.F.S.)
| | - Kamilla de Faria Santos
- Laboratory of Molecular Pathology, Institute of Biological Sciences, Federal University of Goiás (UFG), Goiânia 74690-090, GO, Brazil (K.d.F.S.)
| | - Laura da Silva
- Laboratory of Molecular Pathology, Institute of Biological Sciences, Federal University of Goiás (UFG), Goiânia 74690-090, GO, Brazil (K.d.F.S.)
| | - Caroline Christine Pincela da Costa
- Laboratory of Molecular Pathology, Institute of Biological Sciences, Federal University of Goiás (UFG), Goiânia 74690-090, GO, Brazil (K.d.F.S.)
| | - Rodrigo da Silva Santos
- Laboratory of Molecular Pathology, Institute of Biological Sciences, Federal University of Goiás (UFG), Goiânia 74690-090, GO, Brazil (K.d.F.S.)
- Department of Biochemistry and Molecular Biology, Institute of Biological Sciences, Federal University of Goiás (UFG), Goiânia 74690-090, GO, Brazil
| | - Angela Adamski da Silva Reis
- Laboratory of Molecular Pathology, Institute of Biological Sciences, Federal University of Goiás (UFG), Goiânia 74690-090, GO, Brazil (K.d.F.S.)
- Department of Biochemistry and Molecular Biology, Institute of Biological Sciences, Federal University of Goiás (UFG), Goiânia 74690-090, GO, Brazil
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Elhag DA, Al Khodor S. Exploring the potential of microRNA as a diagnostic tool for gestational diabetes. J Transl Med 2023; 21:392. [PMID: 37330548 PMCID: PMC10276491 DOI: 10.1186/s12967-023-04269-2] [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: 04/26/2023] [Accepted: 06/11/2023] [Indexed: 06/19/2023] Open
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in regulating host gene expression. Recent studies have indicated a role of miRNAs in the pathogenesis of gestational diabetes mellitus (GDM), a common pregnancy-related disorder characterized by impaired glucose metabolism. Aberrant expression of miRNAs has been observed in the placenta and/or maternal blood of GDM patients, suggesting their potential use as biomarkers for early diagnosis and prognosis. Additionally, several miRNAs have been shown to modulate key signaling pathways involved in glucose homeostasis, insulin sensitivity, and inflammation, providing insights into the pathophysiology of GDM. This review summarizes the current knowledge on the dynamics of miRNA in pregnancy, their role in GDM as well as their potential as diagnostic and therapeutic targets.
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Affiliation(s)
- Duaa Ahmed Elhag
- Maternal and Child Health Division, Research Branch, Sidra Medicine, Doha, Qatar
| | - Souhaila Al Khodor
- Maternal and Child Health Division, Research Branch, Sidra Medicine, Doha, Qatar.
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Li J, Gan B, Lu L, Chen L, Yan J. Expression of microRNAs in patients with gestational diabetes mellitus: a systematic review and meta-analysis. Acta Diabetol 2023; 60:461-469. [PMID: 36527500 PMCID: PMC10033571 DOI: 10.1007/s00592-022-02005-8] [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: 09/21/2022] [Accepted: 11/03/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND MicroRNAs (miRNA) are noncoding RNAs that play a central role in governing various physiological and pathological processes. There are few studies on miRNA involvement in gestational diabetes mellitus (GDM). In this study, we performed a meta-analysis of the miRNA expression profiling from GDM patients. METHODS Guided by the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, we performed a systematic search of the PubMed, Cochrane Library, and EMBASE databases from inception to December 20, 2021, to retrieve the original research studies. All the relevant data were retrieved, analyzed, and summarized. RESULTS Six studies (252 GDM cases and 309 controls) were included and analyzed. The six studies reported the expressions of 21 miRNAs in GDM cases. Of the 21 miRNAs, 12 miRNAs were found to be upregulated, and two were downregulated. The top three most consistently reported upregulated miRNAs were miR-16-5p (mean differences of fold change are 1.25, 95% CI = 0.04-2.46, P = 0.040), miR-19a-3p (mean differences of fold change are 2.90, 95% CI = 1.45-4.35, P = 0.001), and miR-19b-3p (mean differences of fold change are 3.10, 95% CI = 0.94-5.25, P = 0.005). miR-155-5p and miR-21-3p were found to be downregulated. CONCLUSIONS The results indicate that several miRNAs may be used as markers for diabetes gestational diabetes mellitus. In the future, more studies are needed to validate the findings of our study.
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Affiliation(s)
- Jianhua Li
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
| | - Bei Gan
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
| | - Lin Lu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
| | - Lihong Chen
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China.
| | - Jianying Yan
- Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
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Goedecke JH, Pheiffer C, Mendham AE. Environmental exposures are important for type 2 diabetes pathophysiology in sub-Saharan African populations. Reply to Christensen D, Hjort L, Mpagama S et al [letter]. Diabetologia 2023; 66:780-782. [PMID: 36692507 DOI: 10.1007/s00125-022-05859-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 12/05/2022] [Indexed: 01/25/2023]
Affiliation(s)
- Julia H Goedecke
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa.
- South African Medical Research Council/WITS Developmental Pathways for Health Research Unit (DPHRU), Department of Paediatrics, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
- Health through Physical Activity, Lifestyle and Sport Research Centre (HPALS), FIMS International Collaborating Centre of Sports Medicine, Division of Physiological Sciences, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
| | - Carmen Pheiffer
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa
| | - Amy E Mendham
- South African Medical Research Council/WITS Developmental Pathways for Health Research Unit (DPHRU), Department of Paediatrics, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Health through Physical Activity, Lifestyle and Sport Research Centre (HPALS), FIMS International Collaborating Centre of Sports Medicine, Division of Physiological Sciences, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
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Lowe WL. Genetics and Epigenetics: Implications for the Life Course of Gestational Diabetes. Int J Mol Sci 2023; 24:6047. [PMID: 37047019 PMCID: PMC10094577 DOI: 10.3390/ijms24076047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/19/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
Gestational diabetes (GDM) is one of the most common complications of pregnancy, affecting as many as one in six pregnancies. It is associated with both short- and long-term adverse outcomes for the mother and fetus and has important implications for the life course of affected women. Advances in genetics and epigenetics have not only provided new insight into the pathophysiology of GDM but have also provided new approaches to identify women at high risk for progression to postpartum cardiometabolic disease. GDM and type 2 diabetes share similarities in their pathophysiology, suggesting that they also share similarities in their genetic architecture. Candidate gene and genome-wide association studies have identified susceptibility genes that are shared between GDM and type 2 diabetes. Despite these similarities, a much greater effect size for MTNR1B in GDM compared to type 2 diabetes and association of HKDC1, which encodes a hexokinase, with GDM but not type 2 diabetes suggest some differences in the genetic architecture of GDM. Genetic risk scores have shown some efficacy in identifying women with a history of GDM who will progress to type 2 diabetes. The association of epigenetic changes, including DNA methylation and circulating microRNAs, with GDM has also been examined. Targeted and epigenome-wide approaches have been used to identify DNA methylation in circulating blood cells collected during early, mid-, and late pregnancy that is associated with GDM. DNA methylation in early pregnancy had some ability to identify women who progressed to GDM, while DNA methylation in blood collected at 26-30 weeks gestation improved upon the ability of clinical factors alone to identify women at risk for progression to abnormal glucose tolerance post-partum. Finally, circulating microRNAs and long non-coding RNAs that are present in early or mid-pregnancy and associated with GDM have been identified. MicroRNAs have also proven efficacious in predicting both the development of GDM as well as its long-term cardiometabolic complications. Studies performed to date have demonstrated the potential for genetic and epigenetic technologies to impact clinical care, although much remains to be done.
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Affiliation(s)
- William L Lowe
- Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Rubloff 12, 420 E. Superior Street, Chicago, IL 60611, USA
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Cardiovascular Disease-Associated MicroRNAs as Novel Biomarkers of First-Trimester Screening for Gestational Diabetes Mellitus in the Absence of Other Pregnancy-Related Complications. Int J Mol Sci 2022; 23:ijms231810635. [PMID: 36142536 PMCID: PMC9501303 DOI: 10.3390/ijms231810635] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/08/2022] [Accepted: 09/09/2022] [Indexed: 11/25/2022] Open
Abstract
We assessed the diagnostic potential of cardiovascular disease-associated microRNAs for the early prediction of gestational diabetes mellitus (GDM) in singleton pregnancies of Caucasian descent in the absence of other pregnancy-related complications. Whole peripheral venous blood samples were collected within 10 to 13 weeks of gestation. This retrospective study involved all pregnancies diagnosed with only GDM (n = 121) and 80 normal term pregnancies selected with regard to equality of sample storage time. Gene expression of 29 microRNAs was assessed using real-time RT-PCR. Upregulation of 11 microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-181a-5p, miR-195-5p, miR-499a-5p, and miR-574-3p) was observed in pregnancies destinated to develop GDM. Combined screening of all 11 dysregulated microRNAs showed the highest accuracy for the early identification of pregnancies destinated to develop GDM. This screening identified 47.93% of GDM pregnancies at a 10.0% false positive rate (FPR). The predictive model for GDM based on aberrant microRNA expression profile was further improved via the implementation of clinical characteristics (maternal age and BMI at early stages of gestation and an infertility treatment by assisted reproductive technology). Following this, 69.17% of GDM pregnancies were identified at a 10.0% FPR. The effective prediction model specifically for severe GDM requiring administration of therapy involved using a combination of these three clinical characteristics and three microRNA biomarkers (miR-20a-5p, miR-20b-5p, and miR-195-5p). This model identified 78.95% of cases at a 10.0% FPR. The effective prediction model for GDM managed by diet only required the involvement of these three clinical characteristics and eight microRNA biomarkers (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-100-5p, miR-125b-5p, miR-195-5p, miR-499a-5p, and miR-574-3p). With this, the model identified 50.50% of GDM pregnancies managed by diet only at a 10.0% FPR. When other clinical variables such as history of miscarriage, the presence of trombophilic gene mutations, positive first-trimester screening for preeclampsia and/or fetal growth restriction by the Fetal Medicine Foundation algorithm, and family history of diabetes mellitus in first-degree relatives were included in the GDM prediction model, the predictive power was further increased at a 10.0% FPR (72.50% GDM in total, 89.47% GDM requiring therapy, and 56.44% GDM managed by diet only). Cardiovascular disease-associated microRNAs represent promising early biomarkers to be implemented into routine first-trimester screening programs with a very good predictive potential for GDM.
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Lu W, Hu C. Molecular biomarkers for gestational diabetes mellitus and postpartum diabetes. Chin Med J (Engl) 2022; 135:1940-1951. [PMID: 36148588 PMCID: PMC9746787 DOI: 10.1097/cm9.0000000000002160] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Indexed: 11/25/2022] Open
Abstract
ABSTRACT Gestational diabetes mellitus (GDM) is a growing public health problem worldwide that threatens both maternal and fetal health. Identifying individuals at high risk for GDM and diabetes after GDM is particularly useful for early intervention and prevention of disease progression. In the last decades, a number of studies have used metabolomics, genomics, and proteomic approaches to investigate associations between biomolecules and GDM progression. These studies clearly demonstrate that various biomarkers reflect pathological changes in GDM. The established markers have potential use as screening and diagnostic tools in GDM and in postpartum diabetes research. In the present review, we summarize recent studies of metabolites, single-nucleotide polymorphisms, microRNAs, and proteins associated with GDM and its transition to postpartum diabetes, with a focus on their predictive value in screening and diagnosis.
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Affiliation(s)
- Wenqian Lu
- Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510630, China
- Department of Endocrinology and Metabolism, Fengxian Central Hospital Affiliated to the Southern Medical University, Shanghai 201400, China
| | - Cheng Hu
- Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510630, China
- Department of Endocrinology and Metabolism, Fengxian Central Hospital Affiliated to the Southern Medical University, Shanghai 201400, China
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The Mystery of Exosomes in Gestational Diabetes Mellitus. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:2169259. [PMID: 35720179 PMCID: PMC9200544 DOI: 10.1155/2022/2169259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 05/31/2022] [Indexed: 11/27/2022]
Abstract
Gestational diabetes mellitus (GDM) is one of the common pregnancy complications, which increases the risk of short-term and long-term adverse consequences in both the mother and offspring. However, the pathophysiological mechanism of GDM is still poorly understood. Inflammation, insulin resistance and oxidative stress are considered critical factors in the occurrence and development of GDM. Although the lifestyle intervention and insulin are the primary treatment, adverse pregnancy outcomes still cannot be ignored. Exosomes have a specific function of carrying biological information, which can transmit information to target cells and play an essential role in intercellular communication. Their possible roles in normal pregnancy and GDM have been widely concerned. The possibility of exosomal cargos as biomarkers of GDM is proposed. This paper reviews the literature in recent years and discusses the role of exosomes in GDM and their possible mechanisms to provide some reference for the prediction, prevention, and treatment of GDM and improve the outcome of pregnancy.
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Li Y, Wen J, Liang D, Sun H. Extracellular Vesicles and Their Associated miRNAs as Potential Biomarkers in Intracranial Aneurysm. Front Mol Biosci 2022; 9:785314. [PMID: 35795823 PMCID: PMC9252459 DOI: 10.3389/fmolb.2022.785314] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 05/30/2022] [Indexed: 11/30/2022] Open
Abstract
Intracranial aneurysms (IA) are abnormal expansions of the intracranial arteries. Once it ruptures, the mortality and disability rate are high. The cost of imaging examinations is high, and rupture risk cannot be predicted, making it difficult for high-risk groups to be screened and prevented. Thus, clinically effective biomarkers are required to screen high-risk groups, estimate the risk of rupture, and determine the appropriate early intervention step. This article introduces the current research and application of exosome-derived microRNA (miRNA) as biomarkers of intracranial aneurysms and their limitations, which can give researchers a general overview of the research in this field. It can also serve as a reference point for selecting related research directions.
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Affiliation(s)
- Yuman Li
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital and the Second Clinical Medical College, Southern Medical University, Guangzhou, China
- Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Jiahao Wen
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital and the Second Clinical Medical College, Southern Medical University, Guangzhou, China
- Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Dingyue Liang
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital and the Second Clinical Medical College, Southern Medical University, Guangzhou, China
- Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Haitao Sun
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital and the Second Clinical Medical College, Southern Medical University, Guangzhou, China
- Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Key Laboratory of Mental Health of the Ministry of Education, Guangdong–Hong Kong–Macao Greater Bay Area Center for Brain Science and Brain–Inspired Intelligence, Southern Medical University, Guangzhou, China
- *Correspondence: Haitao Sun,
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18
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Coetzee A, Hall DR, Conradie M. Hyperglycemia First Detected in Pregnancy in South Africa: Facts, Gaps, and Opportunities. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2022; 3:895743. [PMID: 36992779 PMCID: PMC10012101 DOI: 10.3389/fcdhc.2022.895743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 04/01/2022] [Indexed: 06/19/2023]
Abstract
This review contextualizes hyperglycemia in pregnancy from a South-African perspective. It aims to create awareness of the importance of hyperglycemia in pregnancy in low-middle-income countries. We address unanswered questions to guide future research on sub-Saharan African women with hyperglycemia first detected in pregnancy (HFDP). South African women of childbearing age have the highest prevalence of obesity in sub-Saharan Africa. They are predisposed to Type 2 diabetes (T2DM), the leading cause of death in South African women. T2DM remains undiagnosed in many African countries, with two-thirds of people living with diabetes unaware. With the South African health policy's increased focus on improving antenatal care, women often gain access to screening for non-communicable diseases for the first time in pregnancy. While screening practices and diagnostic criteria for gestational diabetes mellitus (GDM) differ amongst geographical areas in South Africa (SA), hyperglycemia of varying degrees is often first detected in pregnancy. This is often erroneously ascribed to GDM, irrespective of the degree of hyperglycemia and not overt diabetes. T2DM and GDM convey a graded increased risk for the mother and fetus during and after pregnancy, with cardiometabolic risk accumulating across the lifespan. Resource limitations and high patient burden have hampered the opportunity to implement accessible preventative care in young women at increased risk of developing T2DM in the broader public health system in SA. All women with HFDP, including those with true GDM, should be followed and undergo glucose assessment postpartum. In SA, studies conducted early postpartum have noted persistent hyperglycemia in a third of women after GDM. Interpregnancy care is advantageous and may attain a favourable metabolic legacy in these young women, but the yield of return following delivery is suboptimal. We review the current best evidence regarding HFDP and contextualize the applicability in SA and other African or low-middle-income countries. The review identifies gaps and shares pragmatic solutions regarding clinical factors that may improve awareness, identification, diagnosis, and management of women with HFDP.
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Affiliation(s)
- Ankia Coetzee
- Department of Medicine, Division of Endocrinology Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa
| | - David R. Hall
- Department of Obstetrics and Gynecology, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa
| | - Magda Conradie
- Department of Medicine, Division of Endocrinology Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa
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Filardi T, Catanzaro G, Grieco GE, Splendiani E, Trocchianesi S, Santangelo C, Brunelli R, Guarino E, Sebastiani G, Dotta F, Morano S, Ferretti E. Identification and Validation of miR-222-3p and miR-409-3p as Plasma Biomarkers in Gestational Diabetes Mellitus Sharing Validated Target Genes Involved in Metabolic Homeostasis. Int J Mol Sci 2022; 23:ijms23084276. [PMID: 35457094 PMCID: PMC9028517 DOI: 10.3390/ijms23084276] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/08/2022] [Accepted: 04/11/2022] [Indexed: 12/16/2022] Open
Abstract
Gestational diabetes mellitus (GDM) causes both maternal and fetal adverse outcomes. The deregulation of microRNAs (miRNAs) in GDM suggests their involvement in GDM pathogenesis and complications. Exosomes are extracellular vesicles (EVs) of endosomal origin, released via exocytosis into the extracellular compartment. Through EVs, miRNAs are delivered in distant target cells and are able to affect gene expression. In this study, miRNA expression was analyzed to find new miRNAs that could improve GDM classification and molecular characterization. MiRNA were profiled in total plasma and EVs in GDM patients and normal glucose tolerance (NGT) women. Samples were collected at third trimester of gestation from two diabetes centers. MiRNA expression was profiled in a discovery cohort using the multiplexed NanoString nCounter Human v3 miRNA. Validation analysis was performed in a second independent cohort using RT-qPCR. A set of miRNAs resulted to be differentially expressed (DE) in total plasma and EVs in GDM. Among them, total plasma miR-222-3p and miR-409-3p were validated in the independent cohort. MiR-222-3p levels correlated with fasting plasma glucose (FPG) (p < 0.001) and birth weight (p = 0.012), whereas miR-409-3p expression correlated with FPG (p < 0.001) and inversely with gestational age (p = 0.001). The major validated target genes of the deregulated miRNAs were consistently linked to type 2 diabetes and GDM pathophysiology. MiR-222-3p and miR-409-3p are two circulating biomarkers that could improve GDM classification power and act in the context of the molecular events leading to the metabolic alterations observed in GDM.
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Affiliation(s)
- Tiziana Filardi
- Department of Experimental Medicine, “Sapienza” University, 00161 Rome, Italy; (T.F.); (S.M.); (E.F.)
| | - Giuseppina Catanzaro
- Department of Experimental Medicine, “Sapienza” University, 00161 Rome, Italy; (T.F.); (S.M.); (E.F.)
- Correspondence:
| | - Giuseppina Emanuela Grieco
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy; (G.E.G.); (G.S.); (F.D.)
- Fondazione Umberto di Mario, Toscana Life Sciences, 53100 Siena, Italy
| | - Elena Splendiani
- Department of Molecular Medicine, “Sapienza” University, 00161 Rome, Italy; (E.S.); (S.T.)
| | - Sofia Trocchianesi
- Department of Molecular Medicine, “Sapienza” University, 00161 Rome, Italy; (E.S.); (S.T.)
| | - Carmela Santangelo
- Center for Gender-Specific Medicine, Gender Specific Prevention and Health Unit, Istituto Superiore di Sanità, 00161 Rome, Italy;
| | - Roberto Brunelli
- Maternal and Child Health and Urological Sciences, “Sapienza” University, 00161 Rome, Italy;
| | - Elisa Guarino
- UOC Diabetologia, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy;
| | - Guido Sebastiani
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy; (G.E.G.); (G.S.); (F.D.)
- Fondazione Umberto di Mario, Toscana Life Sciences, 53100 Siena, Italy
| | - Francesco Dotta
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy; (G.E.G.); (G.S.); (F.D.)
- Fondazione Umberto di Mario, Toscana Life Sciences, 53100 Siena, Italy
- UOC Diabetologia, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy;
- Tuscany Centre for Precision Medicine (CReMeP), 53100 Siena, Italy
| | - Susanna Morano
- Department of Experimental Medicine, “Sapienza” University, 00161 Rome, Italy; (T.F.); (S.M.); (E.F.)
| | - Elisabetta Ferretti
- Department of Experimental Medicine, “Sapienza” University, 00161 Rome, Italy; (T.F.); (S.M.); (E.F.)
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Juchnicka I, Kuźmicki M, Niemira M, Bielska A, Sidorkiewicz I, Zbucka-Krętowska M, Krętowski AJ, Szamatowicz J. miRNAs as Predictive Factors in Early Diagnosis of Gestational Diabetes Mellitus. Front Endocrinol (Lausanne) 2022; 13:839344. [PMID: 35340328 PMCID: PMC8948421 DOI: 10.3389/fendo.2022.839344] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 02/07/2022] [Indexed: 12/14/2022] Open
Abstract
Introduction Circulating miRNAs are important mediators in epigenetic changes. These non-coding molecules regulate post-transcriptional gene expression by binding to mRNA. As a result, they influence the development of many diseases, such as gestational diabetes mellitus (GDM). Therefore, this study investigates the changes in the miRNA profile in GDM patients before hyperglycemia appears. Materials and Methods The study group consisted of 24 patients with GDM, and the control group was 24 normoglycemic pregnant women who were matched for body mass index (BMI), age, and gestational age. GDM was diagnosed with an oral glucose tolerance test between the 24th and 26th weeks of pregnancy. The study had a prospective design, and serum for analysis was obtained in the first trimester of pregnancy. Circulating miRNAs were measured using the NanoString quantitative assay platform. Validation with real time-polymerase chain reaction (RT-PCR) was performed on the same group of patients. Mann-Whitney U-test and Spearman correlation were done to assess the significance of the results. Results Among the 800 miRNAs, 221 miRNAs were not detected, and 439 were close to background noise. The remaining miRNAs were carefully investigated for their average counts, fold changes, p-values, and false discovery rate (FDR) scores. We selected four miRNAs for further validation: miR-16-5p, miR-142-3p, miR-144-3p, and miR-320e, which showed the most prominent changes between the studied groups. The validation showed up-regulation of miR-16-5p (p<0.0001), miR-142-3p (p=0.001), and miR-144-3p (p=0.003). Conclusion We present changes in miRNA profile in the serum of GDM women, which may indicate significance in the pathophysiology of GDM. These findings emphasize the role of miRNAs as a predictive factor that could potentially be useful in early diagnosis.
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Affiliation(s)
- Ilona Juchnicka
- Department of Gynecology and Gynecological Oncology, Medical University of Bialystok, Bialystok, Poland
| | - Mariusz Kuźmicki
- Department of Gynecology and Gynecological Oncology, Medical University of Bialystok, Bialystok, Poland
| | - Magdalena Niemira
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Agnieszka Bielska
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Iwona Sidorkiewicz
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Monika Zbucka-Krętowska
- Department of Gynecological Endocrinology and Adolescent Gynecology, Medical University of Bialystok, Bialystok, Poland
| | | | - Jacek Szamatowicz
- Department of Gynecology and Gynecological Oncology, Medical University of Bialystok, Bialystok, Poland
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Choi Y, Hong SH. Genetic association between miR‑27a and miR‑449b polymorphisms and susceptibility to diabetes mellitus. Biomed Rep 2022; 16:37. [DOI: 10.3892/br.2022.1520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 02/10/2022] [Indexed: 11/05/2022] Open
Affiliation(s)
- Youngmi Choi
- Department of Science Education, Teachers College, Jeju National University, Jeju 63294, Republic of Korea
| | - Seung-Ho Hong
- Department of Science Education, Teachers College, Jeju National University, Jeju 63294, Republic of Korea
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22
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Sørensen AE, van Poppel MNM, Desoye G, Simmons D, Damm P, Jensen DM, Dalgaard LT. The Temporal Profile of Circulating miRNAs during Gestation in Overweight and Obese Women with or without Gestational Diabetes Mellitus. Biomedicines 2022; 10:biomedicines10020482. [PMID: 35203692 PMCID: PMC8962411 DOI: 10.3390/biomedicines10020482] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 02/10/2022] [Accepted: 02/14/2022] [Indexed: 12/12/2022] Open
Abstract
Circulating non-coding microRNAs (miRNAs) are important for placentation, but their expression profiles across gestation in pregnancies, which are complicated by gestational diabetes mellitus (GDM), have not been fully established. Investigating a single time point is insufficient, as pregnancy is dynamic, involving several processes, including placenta development, trophoblast proliferation and differentiation and oxygen sensing. Thus, the aim of this study was to compare the temporal expression of serum miRNAs in pregnant women with and without GDM. This is a nested case-control study of longitudinal data obtained from a multicentric European study (the ‘DALI’ study). All women (n = 82) were overweight/obese (BMI ≥ 29 kg/m2) and were normal glucose tolerant (NGT) at baseline (before 20 weeks of gestation). We selected women (n = 41) who were diagnosed with GDM at 24–28 weeks, according to the IADPSG/WHO2013 criteria. They were matched with 41 women who remained NGT in their pregnancy. miRNA (miR-16-5p, -29a-3p, -103-3p, -134-5p, -122-5p, -223-3p, -330-3p and miR-433-3p) were selected based on their suggested importance for placentation, and measurements were performed at baseline and at 24–28 and 35–37 weeks of gestation. Women with GDM presented with overall miRNA levels above those observed for women remaining NGT. In both groups, levels of miR-29a-3p and miR-134-5p increased consistently with progressing gestation. The change over time only differed for miR-29a-3p when comparing women with GDM with those remaining NGT (p = 0.044). Our findings indicate that among overweight/obese women who later develop GDM, miRNA levels are already elevated early in pregnancy and remain above those of women who remain NGT during their pregnancy. Maternal circulating miRNAs may provide further insight into placentation and the cross talk between the maternal and fetal compartments.
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Affiliation(s)
- Anja Elaine Sørensen
- Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark;
- Correspondence: ; Tel.: +45-4674-3994
| | - Mireille N. M. van Poppel
- Faculty of Environmental and Regional Sciences and Education, Institute of Human Movement Science, Sport and Health, University of Graz, 8010 Graz, Austria;
| | - Gernot Desoye
- Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria;
- Center for Pregnant Women with Diabetes, Department of Obstetrics, Rigshospitalet, 2100 Copenhagen, Denmark;
| | - David Simmons
- Macarthur Clinical School, School of Medicine, Western Sydney University, Campbelltown, NSE 2560, Australia;
| | - Peter Damm
- Center for Pregnant Women with Diabetes, Department of Obstetrics, Rigshospitalet, 2100 Copenhagen, Denmark;
- Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Dorte Møller Jensen
- Department of Gynecology and Obstetrics, Odense University Hospital, 5000 Odense, Denmark;
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark
- Steno Diabetes Center Odense, Department of Gynecology and Obstetrics, Odense University Hospital, 5000 Odense, Denmark
| | - Louise Torp Dalgaard
- Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark;
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Yang X, Wu N. MicroRNAs and Exosomal microRNAs May Be Possible Targets to Investigate in Gestational Diabetes Mellitus. Diabetes Metab Syndr Obes 2022; 15:321-330. [PMID: 35140490 PMCID: PMC8820256 DOI: 10.2147/dmso.s330323] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Accepted: 01/11/2022] [Indexed: 12/30/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is defined as glucose intolerance that occurs during the second or third trimester of pregnancy. As the incidence of GDM rises, so does the risk of maternal and fetal complications with short- and long-term consequences. As a result, early diagnosis and treatment of this condition are important to avoiding adverse pregnancy outcomes. Exosomes are tiny vesicles secreted by living cells which contain a variety of bioactive substances. They are released by cells to facilitate cell-to-cell communication and regulate a variety of biological processes such as cellular immune response, inflammatory response, and apoptosis, among others. Many studies have recently confirmed that changes in the expression and secretion of exosomal miRNAs can be used as novel markers for the diagnosis, prognosis, and treatment of GDM. In this review, we summarized the various roles of exosomal miRNAs and circulating miRNAs in GDM. We found that the changes in the expression of certain miRNAs could be used to diagnosing GDM. Exosomal miRNAs target metabolic pathways, resulting in insulin resistance. We also highlighted the potential for miRNAs and exosomal miRNAs to be used as biomarkers for diagnosis or therapeutic agents.
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Affiliation(s)
- Xiyao Yang
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
| | - Na Wu
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
- Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
- Correspondence: Na Wu, Department of Endocrinology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Heping District, Shenyang, Liaoning Province, 110004, People’s Republic of China, Tel +86 18940258445, Email
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Lewis KA, Chang L, Cheung J, Aouizerat BE, Jelliffe-Pawlowski LL, McLemore MR, Piening B, Rand L, Ryckman KK, Flowers E. Systematic review of transcriptome and microRNAome associations with gestational diabetes mellitus. Front Endocrinol (Lausanne) 2022; 13:971354. [PMID: 36704034 PMCID: PMC9871895 DOI: 10.3389/fendo.2022.971354] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 12/20/2022] [Indexed: 01/11/2023] Open
Abstract
PURPOSE Gestational diabetes (GDM) is associated with increased risk for preterm birth and related complications for both the pregnant person and newborn. Changes in gene expression have the potential to characterize complex interactions between genetic and behavioral/environmental risk factors for GDM. Our goal was to summarize the state of the science about changes in gene expression and GDM. DESIGN The systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS PubMed articles about humans, in English, from any date were included if they described mRNA transcriptome or microRNA findings from blood samples in adults with GDM compared with adults without GDM. RESULTS Sixteen articles were found representing 1355 adults (n=674 with GDM, n=681 controls) from 12 countries. Three studies reported transcriptome results and thirteen reported microRNA findings. Identified pathways described various aspects of diabetes pathogenesis, including glucose and insulin signaling, regulation, and transport; natural killer cell mediated cytotoxicity; and fatty acid biosynthesis and metabolism. Studies described 135 unique miRNAs that were associated with GDM, of which eight (miR-16-5p, miR-17-5p, miR-20a-5p, miR-29a-3p, miR-195-5p, miR-222-3p, miR-210-3p, and miR-342-3p) were described in 2 or more studies. Findings suggest that miRNA levels vary based on the time in pregnancy when GDM develops, the time point at which they were measured, sex assigned at birth of the offspring, and both the pre-pregnancy and gestational body mass index of the pregnant person. CONCLUSIONS The mRNA, miRNA, gene targets, and pathways identified in this review contribute to our understanding of GDM pathogenesis; however, further research is warranted to validate previous findings. In particular, longitudinal repeated-measures designs are needed that control for participant characteristics (e.g., weight), use standardized data collection methods and analysis tools, and are sufficiently powered to detect differences between subgroups. Findings may be used to improve early diagnosis, prevention, medication choice and/or clinical treatment of patients with GDM.
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Affiliation(s)
- Kimberly A. Lewis
- School of Nursing, Department of Physiological Nursing, University of California, San Francisco, San Francisco, CA, United States
- *Correspondence: Kimberly A. Lewis,
| | - Lisa Chang
- School of Nursing, Department of Physiological Nursing, University of California, San Francisco, San Francisco, CA, United States
| | - Julinna Cheung
- College of Biological Sciences, University of California at Davis, Davis, CA, United States
| | | | - Laura L. Jelliffe-Pawlowski
- Department of Epidemiology and Biostatistics, School of Medicine, University of California at San Francisco, San Francisco, CA, United States
| | - Monica R. McLemore
- School of Nursing, Department of Family Health Care Nursing, University of California, San Francisco, San Francisco, CA, United States
| | - Brian Piening
- Earle A. Chiles Research Institute, Providence St Joseph Health, Portland, OR, United States
| | - Larry Rand
- Obstetrics and Gynecology, Reproductive Sciences, School of Medicine, University of California at San Francisco, San Francisco, CA, United States
| | - Kelli K. Ryckman
- Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, United States
| | - Elena Flowers
- School of Nursing, Department of Physiological Nursing, University of California, San Francisco, San Francisco, CA, United States
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Légaré C, Desgagné V, Thibeault K, White F, Clément AA, Poirier C, Luo ZC, Scott MS, Jacques PÉ, Perron P, Guérin R, Hivert MF, Bouchard L. First Trimester Plasma MicroRNA Levels Predict Risk of Developing Gestational Diabetes Mellitus. Front Endocrinol (Lausanne) 2022; 13:928508. [PMID: 36440215 PMCID: PMC9693764 DOI: 10.3389/fendo.2022.928508] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 06/23/2022] [Indexed: 11/13/2022] Open
Abstract
AIMS Our objective is to identify first-trimester plasmatic miRNAs associated with and predictive of GDM. METHODS We quantified miRNA using next-generation sequencing in discovery (Gen3G: n = 443/GDM = 56) and replication (3D: n = 139/GDM = 76) cohorts. We have diagnosed GDM using a 75-g oral glucose tolerance test and the IADPSG criteria. We applied stepwise logistic regression analysis among replicated miRNAs to build prediction models. RESULTS We identified 17 miRNAs associated with GDM development in both cohorts. The prediction performance of hsa-miR-517a-3p|hsa-miR-517b-3p, hsa-miR-218-5p, and hsa-let7a-3p was slightly better than GDM classic risk factors (age, BMI, familial history of type 2 diabetes, history of GDM or macrosomia, and HbA1c) (AUC 0.78 vs. 0.75). MiRNAs and GDM classic risk factors together further improved the prediction values [AUC 0.84 (95% CI 0.73-0.94)]. These results were replicated in 3D, although weaker predictive values were obtained. We suggest very low and higher risk GDM thresholds, which could be used to identify women who could do without a diagnostic test for GDM and women most likely to benefit from an early GDM prevention program. CONCLUSIONS In summary, three miRNAs combined with classic GDM risk factors provide excellent prediction values, potentially strong enough to improve early detection and prevention of GDM.
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Affiliation(s)
- Cécilia Légaré
- Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences (FMHS), Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Véronique Desgagné
- Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences (FMHS), Université de Sherbrooke, Sherbrooke, QC, Canada
- Clinical Department of Laboratory Medicine, Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Saguenay–Lac-St-Jean – Hôpital Universitaire de Chicoutimi, Saguenay, QC, Canada
| | - Kathrine Thibeault
- Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences (FMHS), Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Frédérique White
- Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Andrée-Anne Clément
- Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences (FMHS), Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Cédrik Poirier
- Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences (FMHS), Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Zhong Cheng Luo
- Prosserman Centre for Population Health Research, Department of Obstetrics and Gynecology, Mount Sinai Hospital, Faculty of Medicine, Lunenfeld-Tanenbaum Research Institute, University of Toronto, Toronto, ON, Canada
| | - Michelle S. Scott
- Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences (FMHS), Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Pierre-Étienne Jacques
- Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada
- Centre de Recherche du Centre hospitalier universitaire de Sherbrooke (CR-CHUS), Sherbrooke, QC, Canada
| | - Patrice Perron
- Centre de Recherche du Centre hospitalier universitaire de Sherbrooke (CR-CHUS), Sherbrooke, QC, Canada
- Department of Medicine, Faculty of Medicine and Health Sciences (FMHS), Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Renée Guérin
- Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences (FMHS), Université de Sherbrooke, Sherbrooke, QC, Canada
- Clinical Department of Laboratory Medicine, Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Saguenay–Lac-St-Jean – Hôpital Universitaire de Chicoutimi, Saguenay, QC, Canada
| | - Marie-France Hivert
- Department of Medicine, Faculty of Medicine and Health Sciences (FMHS), Université de Sherbrooke, Sherbrooke, QC, Canada
- Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, United States
- Diabetes Unit, Massachusetts General Hospital, Boston, MA, United States
| | - Luigi Bouchard
- Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences (FMHS), Université de Sherbrooke, Sherbrooke, QC, Canada
- Clinical Department of Laboratory Medicine, Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Saguenay–Lac-St-Jean – Hôpital Universitaire de Chicoutimi, Saguenay, QC, Canada
- Centre de Recherche du Centre hospitalier universitaire de Sherbrooke (CR-CHUS), Sherbrooke, QC, Canada
- *Correspondence: Luigi Bouchard,
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26
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Masete M, Dias S, Malaza N, Adam S, Pheiffer C. A Big Role for microRNAs in Gestational Diabetes Mellitus. Front Endocrinol (Lausanne) 2022; 13:892587. [PMID: 35957839 PMCID: PMC9357936 DOI: 10.3389/fendo.2022.892587] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 06/24/2022] [Indexed: 12/16/2022] Open
Abstract
Maternal diabetes is associated with pregnancy complications and poses a serious health risk to both mother and child. Growing evidence suggests that pregnancy complications are more frequent and severe in pregnant women with pregestational type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) compared to women with gestational diabetes mellitus (GDM). Elucidating the pathophysiological mechanisms that underlie the different types of maternal diabetes may lead to targeted strategies to prevent or reduce pregnancy complications. In recent years, microRNAs (miRNAs), one of the most common epigenetic mechanisms, have emerged as key players in the pathophysiology of pregnancy-related disorders including diabetes. This review aims to provide an update on the status of miRNA profiling in pregnancies complicated by maternal diabetes. Four databases, Pubmed, Web of Science, EBSCOhost, and Scopus were searched to identify studies that profiled miRNAs during maternal diabetes. A total of 1800 articles were identified, of which 53 are included in this review. All studies profiled miRNAs during GDM, with no studies on miRNA profiling during pregestational T1DM and T2DM identified. Studies on GDM were mainly focused on the potential of miRNAs to serve as predictive or diagnostic biomarkers. This review highlights the lack of miRNA profiling in pregnancies complicated by T1DM and T2DM and identifies the need for miRNA profiling in all types of maternal diabetes. Such studies could contribute to our understanding of the mechanisms that link maternal diabetes type with pregnancy complications.
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Affiliation(s)
- Matladi Masete
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa
- Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Stephanie Dias
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa
| | - Nompumelelo Malaza
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa
- Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Sumaiya Adam
- Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Carmen Pheiffer
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa
- Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
- Center for Cardio-Metabolic Research in Africa (CARMA), Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa
- *Correspondence: Carmen Pheiffer,
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Valencia-Ortega J, Saucedo R, Sánchez-Rodríguez MA, Cruz-Durán JG, Martínez EGR. Epigenetic Alterations Related to Gestational Diabetes Mellitus. Int J Mol Sci 2021; 22:ijms22179462. [PMID: 34502370 PMCID: PMC8430976 DOI: 10.3390/ijms22179462] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 08/27/2021] [Accepted: 08/28/2021] [Indexed: 02/06/2023] Open
Abstract
Gestational diabetes mellitus (GDM) is the most common metabolic complication in pregnancy, which affects the future health of both the mother and the newborn. Its pathophysiology involves nutritional, hormonal, immunological, genetic and epigenetic factors. Among the latter, it has been observed that alterations in DNA (deoxyribonucleic acid) methylation patterns and in the levels of certain micro RNAs, whether in placenta or adipose tissue, are related to well-known characteristics of the disease, such as hyperglycemia, insulin resistance, inflammation and excessive placental growth. Furthermore, epigenetic alterations of gestational diabetes mellitus are observable in maternal blood, although their pathophysiological roles are completely unknown. Despite this, it has not been possible to determine the causes of the epigenetic characteristics of GDM, highlighting the need for integral and longitudinal studies. Based on this, this article summarizes the most relevant and recent studies on epigenetic alterations in placenta, adipose tissue and maternal blood associated with GDM in order to provide the reader with a general overview of the subject and indicate future research topics.
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Affiliation(s)
- Jorge Valencia-Ortega
- Unidad de Investigación Médica en Enfermedades Endocrinas, UMAE Hospital de Especialidades, Instituto Mexicano del Seguro Social, Mexico City 06600, Mexico;
| | - Renata Saucedo
- Unidad de Investigación Médica en Enfermedades Endocrinas, UMAE Hospital de Especialidades, Instituto Mexicano del Seguro Social, Mexico City 06600, Mexico;
- Correspondence: ; Tel.: +55-55887521
| | - Martha A. Sánchez-Rodríguez
- Unidad de Investigación en Gerontología, Facultad de Estudios Superiores Zaragoza, Universidad Autónoma de México, Mexico City 04510, Mexico;
| | - José G. Cruz-Durán
- UMAE Hospital de Gineco-Obstetricia No. 3, Instituto Mexicano del Seguro Social, Mexico City 06600, Mexico;
| | - Edgar G. Ramos Martínez
- Universidad Autónoma Benito Juárez de Oaxaca and Instituto de Cómputo Aplicado en Ciencias, Oaxaca 68120, Mexico;
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Circulating Nucleic Acids in Maternal Plasma and Serum in Pregnancy Complications: Are They Really Useful in Clinical Practice? A Systematic Review. Mol Diagn Ther 2021; 24:409-431. [PMID: 32367458 DOI: 10.1007/s40291-020-00468-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE A systematic review was carried out to summarize the available evidence to assess whether circulating nucleic acids in maternal plasma and serum (CNAPS) have the potential to serve as extra and independent markers for the prediction and/or progression monitoring of the most common and severe complications of pregnancy, including preeclampsia, intrauterine growth restriction, preterm delivery, morbidly adherent placenta, gestational diabetes, antiphospholipid syndrome, threatened abortion, intrahepatic cholestasis of pregnancy, and hyperemesis gravidarum. METHOD A comprehensive literature search of the MEDLINE (PubMed), EMBASE, and ISI Web of Knowledge databases was conducted to identify relevant studies that included amounts of CNAPS in the abovementioned pregnancy complications. RESULTS Eighty-three studies met the eligibility criteria. The vast majority of studies were conducted on the quantity of total circulating cell free DNA (cfDNA) and cell free fetal DNA (cffDNA), and some were conducted on messenger RNA (mRNA) species. A few studies have instead evaluated the cell free DNA fetal fraction (cfDNAff), but only in a limited number of pregnancy complications. Despite the growing interest and the abundance of the papers available, little information is available for other new CNAPS, including microRNA (miRNA), long noncoding RNA (lncRNA), mitochondrial DNA (mtDNA), and circular RNA. CONCLUSION Due to the heterogeneity of the populations enrolled, the scarcity of the studies that adjusted the CNAPS values for possible confounding factors, and the difficulty in interpreting the published data, no conclusion regarding the statistical robustness and clinical relevance of the data can be made at present. If assayed at the third trimester, the CNAPS have, however, shown better performance, and could be used in populations already at risk of developing complications as suggested by the presence of other clinical features. Other CNAPS, including miRNA, are under investigation, especially for the screening of gestational diabetes mellitus, but no data about their clinical utility are available. Circulating DNA (cfDNA, cffDNA, and cfDNAff) and mRNA have not been properly evaluated yet, especially in patients asymptomatic early in pregnancy but who developed complications later, perhaps because of the high cost of these techniques and the availability of other predictors of pregnancy complications (biochemical, biophysical, and ultrasound markers). Therefore, from the analysis of the data, the positive predictive value is not available. As regards the new CNAPS, including miRNA, there are still no sufficient data to understand if they can be promising markers for pregnancy complications monitoring and screening, since CNAPS are statistically weak and expensive. It is reasonable to currently conclude that the use of the CNAPS in clinical practice is not recommended.
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Hua Z, Li D, Wu A, Cao T, Luo S. miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus. Open Med (Wars) 2021; 16:464-471. [PMID: 33817324 PMCID: PMC8005781 DOI: 10.1515/med-2021-0247] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 01/07/2021] [Accepted: 02/09/2021] [Indexed: 12/30/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is a metabolic dysregulation closely related to both obesity and type 2 diabetes; however, the molecular mechanism underlying GDM is still unclear. The purpose of this study was to investigate the effects of microRNA-377 (miR-377-3p) and fibronectin type III domain containing 5 (FNDC5) in regulating the cell growth of trophoblasts under high glucose (HG) conditions during the development of GDM. Serum miR-377-3p was upregulated and positively correlated with fasting blood glucose level in GDM patients. miR-377-3p downregulation increased the cell vitality and suppressed the cell apoptosis of HG-treated HTR-8/SVneo and BeWo cells. Using TargetScan prediction, luciferase assay, and western blot, it was found that miR-377-3p could target FNDC5 and suppress its expression. However, FNDC5 downregulation abolished the effect of miR-377-3p inhibitor in HTR-8/SVneo cells. Together, miR-377 is a potential target for GDM biomarker, which promotes cell growth and suppresses cell apoptosis, partly through the upregulation of FNDC5.
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Affiliation(s)
- Zhaozhao Hua
- Department of Obstetrics, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 83 Feishan Street, Yunyan District, Guiyang City, Guizhou Province, 550003, China
| | - Dana Li
- Department of Obstetrics, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 83 Feishan Street, Yunyan District, Guiyang City, Guizhou Province, 550003, China
| | - Anqin Wu
- Department of Obstetrics, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 83 Feishan Street, Yunyan District, Guiyang City, Guizhou Province, 550003, China
| | - Ting Cao
- Department of Obstetrics, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 83 Feishan Street, Yunyan District, Guiyang City, Guizhou Province, 550003, China
| | - Shi Luo
- Department of Obstetrics, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 83 Feishan Street, Yunyan District, Guiyang City, Guizhou Province, 550003, China
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30
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Wang H. MicroRNAs, Parkinson's Disease, and Diabetes Mellitus. Int J Mol Sci 2021; 22:ijms22062953. [PMID: 33799467 PMCID: PMC8001823 DOI: 10.3390/ijms22062953] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/08/2021] [Accepted: 03/09/2021] [Indexed: 02/07/2023] Open
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder that affects 1% of the population over the age of 60. Diabetes Mellitus (DM) is a metabolic disorder that affects approximately 25% of adults over the age of 60. Recent studies showed that DM increases the risk of developing PD. The link between DM and PD has been discussed in the literature in relation to different mechanisms including mitochondrial dysfunction, oxidative stress, and protein aggregation. In this paper, we review the common microRNA (miRNA) biomarkers of both diseases. miRNAs play an important role in cell differentiation, development, the regulation of the cell cycle, and apoptosis. They are also involved in the pathology of many diseases. miRNAs can mediate the insulin pathway and glucose absorption. miRNAs can also regulate PD-related genes. Therefore, exploring the common miRNA biomarkers of both PD and DM can shed a light on how these two diseases are correlated, and targeting miRNAs is a potential therapeutic opportunity for both diseases.
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Affiliation(s)
- Hsiuying Wang
- Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan
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31
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Hocaoglu M, Demirer S, Loclar Karaalp I, Kaynak E, Attar E, Turgut A, Karateke A, Komurcu-Bayrak E. Identification of miR-16-5p and miR-155-5p microRNAs differentially expressed in circulating leukocytes of pregnant women with polycystic ovary syndrome and gestational diabetes. Gynecol Endocrinol 2021; 37:216-220. [PMID: 33148068 DOI: 10.1080/09513590.2020.1843620] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Pregnant women with polycystic ovary syndrome (PCOS) are at increased risk of gestational diabetes (GDM). We aimed to assess the expressions of candidate microRNAs (miRs) in leukocytes of pregnant women with PCOS and GDM. Methods: Using real-time quantitative PCR method, miR-16-5p and miR-155-5p were examined from PCOS (n = 17), GDM (n = 14), GDM + PCOS (n = 11), and controls (n = 27). The relative expression levels of the candidate miRNAs were compared between patient and control samples. The results were calculated as relative quantification values (RQ). Results: After adjusting for potential confounding variables using ANCOVA, no significant differences were observed in miR-16-5p (p = .154) and miR-155-5p (p = .702) expressions among four groups. We found significantly upregulated miR-16-5p expression in PCOS patients (RQ = 12.97 ± 1.94; p = .0001), compared to controls (RQ = 2.32 ± 1.46). Decreased miR-155-5p was found in GDM women (RQ = 0.80 ± 0.36; p = .04), compared to controls (RQ = 1.78 ± 0.25). Body mass index had a positive correlation with 155-5p in the GDM group (r = 0.55; p = .038). We found strong positive correlation between 1-hour glucose and miR-155-5p in PCOS patients (r = 0.71; p = .001). Fasting glucose (r= -0.63, p = .03) presented significant inverse association with miR-16-5p in the GDM + PCOS group. Discussion: The present study shows for the first time that increased miR-16-5p expression is associated with PCOS in pregnancy. Moreover, downregulated miR-155-5p expression was found in relation with GDM.
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Affiliation(s)
- Meryem Hocaoglu
- Department of Obstetrics and Gynecology, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey
| | - Selin Demirer
- Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Ilayda Loclar Karaalp
- Department of Obstetrics and Gynecology, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey
| | - Esra Kaynak
- Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Erkut Attar
- Department of Obstetrics and Gynecology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
| | - Abdulkadir Turgut
- Department of Obstetrics and Gynecology, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey
- Department of Obstetrics and Gynecology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey
| | - Ates Karateke
- Department of Obstetrics and Gynecology, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey
- Department of Obstetrics and Gynecology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey
| | - Evrim Komurcu-Bayrak
- Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
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Liu L, Zhang J, Liu Y. MicroRNA-1323 serves as a biomarker in gestational diabetes mellitus and aggravates high glucose-induced inhibition of trophoblast cell viability by suppressing TP53INP1. Exp Ther Med 2021; 21:230. [PMID: 33603839 PMCID: PMC7851622 DOI: 10.3892/etm.2021.9661] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 12/14/2020] [Indexed: 12/21/2022] Open
Abstract
Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes, and microRNAs (miRNAs/miRs) have been suggested to be associated with GDM, but the pathological mechanisms remain unclear. The present study aimed to investigate the diagnostic value of miR-1323 in GDM patients and its effects on trophoblast cell viability. Additionally, the present study investigated the correlation between miR-1323 and TP53INP1 to understand the pathological mechanism of GDM progression. Reverse transcription-quantitative polymerase chain reaction was used to detect the miR-1323 expression and TP53INP1 mRNA expression. The diagnostic value of serum miR-1323 was evaluated by receiver operating characteristic analysis. HTR-8/SVneo and BeWo cells were treated with high glucose (HG) to construct cell models of GDM, and trophoblast cell viability was assessed using an MTT assay. The protein expression of TP53INP1 was detected by western blot analysis. The correlation between miR-1323 and TP53INP1 was investigated by luciferase reporter assay. The miR-1323 expression was increased in patients with GDM, which had relatively high diagnostic accuracy for GDM screening and was positively correlated with fasting blood glucose in patients GDM. HG upregulated the miR-1323 expression and inhibited trophoblast cell viability. Overexpression of miR-1323 significantly inhibited the viability of HG-induced trophoblast cells. TP53INP1, a target gene of miR-1323, was negatively correlated with miR-1323. TP53INP1 overexpression reversed the inhibitory effect of miR-1323 overexpression on the viability of HG-treated trophoblast cells. Increased levels of serum miR-1323 may be a diagnostic biomarker for GDM. Additionally, miR-1323 may inhibit trophoblast cell viability by inhibiting TP53INP1, suggesting that it may be a potential therapeutic target for GDM.
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Affiliation(s)
- Lijun Liu
- Department of Gynecology, Weifang Maternal and Child Health Hospital, Weifang, Shandong 261011, P.R. China
| | - Jun Zhang
- Department of Pharmacy, Weifang Maternal and Child Health Hospital, Weifang, Shandong 261011, P.R. China
| | - Yujuan Liu
- Department of Central Supply Room, Weifang Maternal and Child Health Hospital, Weifang, Shandong 261011, P.R. China
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The Predictive Value of miR-16, -29a and -134 for Early Identification of Gestational Diabetes: A Nested Analysis of the DALI Cohort. Cells 2021; 10:cells10010170. [PMID: 33467738 PMCID: PMC7830355 DOI: 10.3390/cells10010170] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 01/08/2021] [Accepted: 01/14/2021] [Indexed: 12/13/2022] Open
Abstract
Early identification of gestational diabetes mellitus (GDM) aims to reduce the risk of adverse maternal and perinatal outcomes. Currently, no circulating biomarker has proven clinically useful for accurate prediction of GDM. In this study, we tested if a panel of small non-coding circulating RNAs could improve early prediction of GDM. We performed a nested case-control study of participants from the European multicenter ‘Vitamin D and lifestyle intervention for GDM prevention (DALI)’ trial using serum samples from obese pregnant women (BMI ≥ 29 kg/m2) entailing 82 GDM cases (early- and late- GDM), and 41 age- and BMI-matched women with normal glucose tolerance (NGT) throughout pregnancy (controls). Anthropometric, clinical and biochemical characteristics were obtained at baseline (<20 weeks of gestation) and throughout gestation. Baseline serum microRNAs (miRNAs) were measured using quantitative real time PCR (qPCR). Elevated miR-16-5p, -29a-3p, and -134-5p levels were observed in women, who were NGT at baseline and later developed GDM, compared with controls who remained NGT. A combination of the three miRNAs could distinguish later GDM from NGT cases (AUC 0.717, p = 0.001, compared with fasting plasma glucose (AUC 0.687, p = 0.004)) as evaluated by area under the curves (AUCs) using Receiver Operator Characteristics (ROC) analysis. Elevated levels of individual miRNAs or a combination hereof were associated with higher odds ratios of GDM. Conclusively, circulating miRNAs early in pregnancy could serve as valuable predictive biomarkers of GDM.
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Zhang TN, Wang W, Huang XM, Gao SY. Non-Coding RNAs and Extracellular Vehicles: Their Role in the Pathogenesis of Gestational Diabetes Mellitus. Front Endocrinol (Lausanne) 2021; 12:664287. [PMID: 34093439 PMCID: PMC8173208 DOI: 10.3389/fendo.2021.664287] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 05/06/2021] [Indexed: 12/21/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first recognition in the second or third trimester of pregnancy. GDM has a considerable impact on health outcomes of the mother and offspring during pregnancy, delivery, and beyond. Although the exact mechanism regarding GDM remains unclear, numerous studies have suggested that non-coding RNAs, including long non-coding (lnc)RNAs, microRNAs, and circular RNAs, were involved in the pathogenesis of GDM in which they played vital regulatory roles. Additionally, several studies have revealed that extracellular vehicles also participated in the pathogenesis of GDM, highlighting their important role in this disease. Considering the lack of effective biomarkers for the early identification of and specific treatment for GDM, non-coding RNAs and extracellular vehicles may be promising biomarkers and even targets for GDM therapies. This review provides an update on our understanding of the role of non-coding RNAs and extracellular vehicles in GDM. As our understanding of the function of lncRNAs and extracellular vehicles improves, the future appears promising for their use as potential biomarkers and treatment targets for GDM in clinical practice.
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Affiliation(s)
- Tie-Ning Zhang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Wei Wang
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xin-Mei Huang
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
- *Correspondence: Xin-Mei Huang, ; Shan-Yan Gao,
| | - Shan-Yan Gao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Xin-Mei Huang, ; Shan-Yan Gao,
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Yu J, Fang C, Zhang Z, Zhang G, Shi L, Qian J, Xiong J. H19 Rises in Gastric Cancer and Exerts a Tumor-Promoting Function via miR-138/ E2F2 Axis. Cancer Manag Res 2020; 12:13033-13042. [PMID: 33376397 PMCID: PMC7762430 DOI: 10.2147/cmar.s267357] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 08/13/2020] [Indexed: 12/16/2022] Open
Abstract
Purpose The aim of this paper was to investigate H19 expression in gastric cancer (GC) and its effects on the biological behavior of gastric cancer cells (GCCs), and at exploring its potential mechanism. Methods H19 expression in the patients’ tissues and serum was detected, and the correlation of the expression with the patients’ pathological data and survival rate was analyzed. Overexpression or inhibitory vectors of H19, microRNA-138 (miR-138) and E2F2 were constructed and transfected into GCCs to observe their effects on the cells’ proliferation, invasion and apoptosis. Results H19 rose in GC and was higher in GC patients with a tumor size ≥5 cm, high stages (III+IV) and lymph node metastasis. High H19 expression was associated with the poorer survival rate of the patients, so serum H19 had a certain diagnostic value for GC. H19 knockdown could inhibit GCCs to proliferate and invade and induce their apoptosis. miR-138 can be used as the target gene of H19, and E2F2 can be negatively regulated by this miR, so miR-138 knockdown or E2F2 upregulation can weaken GCCs’ biological behavior changes that were caused by H19 knockdown. Conclusion H19 can be used as a biological indicator for diagnosing GC and predicting patients’ poor prognosis. Additionally, it promotes GCCs to proliferate and invade through miR-138/E2F2 axis.
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Affiliation(s)
- Jingrong Yu
- Department of Oncology, The Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330003, People's Republic of China
| | - Cheng Fang
- Department of Oncology, Nanchang 334 Hospital, Nanchang, Jiangxi Province, People's Republic of China
| | - Ziyue Zhang
- Department of Oncology, Nanchang 334 Hospital, Nanchang, Jiangxi Province, People's Republic of China
| | - Guifang Zhang
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China
| | - Lihong Shi
- Department of Gynecology and Pediatrics, Nanchang 334 Hospital, Nanchang, Jiangxi Province, People's Republic of China
| | - Jiayi Qian
- Department of Ultrasound Electrophysiology, Nanchang 334 Hospital, Nanchang, Jiangxi Province, People's Republic of China
| | - Jianping Xiong
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, People's Republic of China
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Wang H. MicroRNA, Diabetes Mellitus and Colorectal Cancer. Biomedicines 2020; 8:biomedicines8120530. [PMID: 33255227 PMCID: PMC7760221 DOI: 10.3390/biomedicines8120530] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 11/19/2020] [Accepted: 11/23/2020] [Indexed: 12/11/2022] Open
Abstract
Diabetes mellitus (DM) is an endocrinological disorder that is due to either the pancreas not producing enough insulin, or the body does not respond appropriately to insulin. There are many complications of DM such as retinopathy, nephropathy, and peripheral neuropathy. In addition to these complications, DM was reported to be associated with different cancers. In this review, we discuss the association between DM and colorectal cancer (CRC). CRC is the third most commonly diagnosed cancer worldwide that mostly affects older people, however, its incidence and mortality are rising among young people. We discuss the relationship between DM and CRC based on their common microRNA (miRNA) biomarkers. miRNAs are non-coding RNAs playing important functions in cell differentiation, development, regulation of cell cycle, and apoptosis. miRNAs can inhibit cell proliferation and induce apoptosis in CRC cells. miRNAs also can improve glucose tolerance and insulin sensitivity. Therefore, investigating the common miRNA biomarkers of both DM and CRC can shed a light on how these two diseases are correlated and more understanding of the link between these two diseases can help the prevention of both DM and CRC.
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Affiliation(s)
- Hsiuying Wang
- Institute of Statistics, National Chiao Tung University, Hsinchu 30010, Taiwan
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Zhou R, Wang L, Zhao G, Chen D, Song X, Momtazi-Borojeni AA, Yuan H. Circulating exosomal microRNAs as emerging non-invasive clinical biomarkers in heart failure: Mega bio-roles of a nano bio-particle. IUBMB Life 2020; 72:2546-2562. [PMID: 33053610 DOI: 10.1002/iub.2396] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 09/22/2020] [Accepted: 10/02/2020] [Indexed: 12/12/2022]
Abstract
Exosomes are nano-sized extracellular vesicles containing a cell-specific biologically active cargo of proteins and genetic materials. Exosomes are constitutively released from almost all cell-types and affect neighboring or distant cells through a complex intercellular exchange of the genetic information and/or regulation of certain gene expressions that change the function and behavior of recipient cells. Those released into body fluids are the major mediators of intercellular communications. The success of the biological functions of exosomes is highly mediated by the effective transfer of microRNAs (miRs). Exosomes secreted by a damaged or diseased heart can exhibit alterations in the miRs' profile that may reflect the cellular origin and (patho)physiological state, as a "signature" or "fingerprint" of the donor cell. It has been shown that the transportation of cardiac-specific miRs in exosomes can be rapidly detected and measured, holding great potential as biomarkers in heart diseases. Currently, the search for new biomarkers of heart diseases remains a large and increasing enterprise. Notably, circulating exosomal miRs (Exo-miRs) have successfully gained huge interests for their diagnostic and prognostic potentials. The present review highlights circulating Exo-miRs explored for diagnosis/prognosis and outcome prediction in patients with heart failure (HF). To this end, we explain the feasibility of exosomes as clinical biomarkers, discuss the priority of circulating Exo-miRs over non-exosomal ones as a biomarker, and then outline reported circulating Exo-miRs having the biomarker function in HF patients, together with their mechanism of action. In conclusion, circulating Exo-miRs represent emerging diagnostic (Exo-miR-92b-5p, Exo-miR-146a, Exo-miR-181c, and Exo-miR-495) and prognostic (Exo-miR-192, Exo-miR-194, Exo-miR-34a, Exo-miR-425, Exo-miR-744) biomarkers for HF.
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Affiliation(s)
- Runfa Zhou
- Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.,Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Leiyan Wang
- Clinical Skill Training Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Gang Zhao
- Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Dan Chen
- Department of Cardiology Electrocardiogram Room, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Xiaoning Song
- Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.,Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Amir A Momtazi-Borojeni
- Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Haitao Yuan
- Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
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Tu C, Wang L, Tao H, Gu L, Zhu S, Chen X. Expression of miR-409-5p in gestational diabetes mellitus and its relationship with insulin resistance. Exp Ther Med 2020; 20:3324-3329. [PMID: 32855704 PMCID: PMC7444361 DOI: 10.3892/etm.2020.9049] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 06/19/2020] [Indexed: 12/12/2022] Open
Abstract
Expression of miR-409-5p in gestational diabetes mellitus (GDM) and its relationship with insulin resistance were explore. One hundred and forty-nine pregnant women who underwent antenatal examination in Taizhou First People's Hospital were divided into a GDM group and a control group according to whether they had GDM or not. Serum miR-409-5p expression of the two groups was detected, and the levels of glycosylated hemoglobin (HbAlc) and other GDM-related biochemical indicators were measured. Fasting plasma glucose (FPG) was determined by glucose oxidase method, fasting insulin (FINS) was detected by radioimmunoassay, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The relationship between miR-409-5p and other biochemical indicators and insulin resistance was analyzed, and logistic multivariate regression was employed to analyze the risk factors of GDM. miR-409-5p was highly expressed in the serum of GDM patients. HbAlc, FPG, FINS, and HOMA-IR in pregnant women in the GDM group were markedly higher than those in the control group. The serum miR-409-5p in GDM pregnant women showed a positive correlation with HbAlc, FPG, FINS, and HOMA-IR (P<0.05). The insulin resistance group presented remarkably higher serum miR-409-5p level than the non-insulin resistance group. Moreover, it was found that elevated miR-409-5p, FINS, and HOMA-IR were all independent risk factors for the onset of GDM. miR-409-5p is highly expressed in the serum of patients with GDM, and it is positively correlated with insulin resistance index of GDM patients, which may be a potential target for clinical diagnosis and treatment of GDM.
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Affiliation(s)
- Chuanfa Tu
- Department of Endocrinology, Taizhou First People's Hospital, Taizhou, Zhejiang 318020, P.R. China
| | - Lijun Wang
- Department of Endocrinology, Taizhou First People's Hospital, Taizhou, Zhejiang 318020, P.R. China
| | - Haiying Tao
- Department of Endocrinology, Taizhou First People's Hospital, Taizhou, Zhejiang 318020, P.R. China
| | - Lingjia Gu
- Department of Endocrinology, Taizhou First People's Hospital, Taizhou, Zhejiang 318020, P.R. China
| | - Shuang Zhu
- Department of Endocrinology, Taizhou First People's Hospital, Taizhou, Zhejiang 318020, P.R. China
| | - Xiaolu Chen
- Department of Obstetrics and Gynecology, Taizhou First People's Hospital, Taizhou, Zhejiang 318020, P.R. China
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Kim H, Bae YU, Lee H, Kim H, Jeon JS, Noh H, Han DC, Byun DW, Kim SH, Park HK, Ryu S, Kwon SH. Effect of diabetes on exosomal miRNA profile in patients with obesity. BMJ Open Diabetes Res Care 2020; 8:8/1/e001403. [PMID: 32883688 PMCID: PMC7473624 DOI: 10.1136/bmjdrc-2020-001403] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 07/01/2020] [Accepted: 07/21/2020] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Obesity is a risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease. T2DM increases the risk of cardiovascular-related death. We investigated changes in circulating exosomal microRNA (miRNA) profiles in patients with DM with obesity compared with patients without DM with obesity. RESEARCH DESIGN AND METHODS This prospective study involved 29 patients with obesity (patients without DM=16, patients with DM=13) and healthy volunteers (HVs) (n=18). We measured circulating levels of exosomal miRNAs by next-generation sequencing and compared miRNA levels across the three groups. RESULTS The expression levels of 25 miRNAs (upregulated=14, downregulated=11) differed between patients with obesity with DM and patients with obesity without DM. Compared with HV, patients with DM with obesity had 53 dysregulated miRNAs. Additionally, moving stepwise from HV to patients with obesity without DM to patients with obesity with DM, there was a consistent increase in expression levels of miR-23a-5p and miR-6087 and a consistent decrease in expressions levels of miR-6751-3p. CONCLUSIONS Our data show that the exosomal miRNAs is altered by dysregulated glucose metabolism in patients with obesity. This circulating exosomal miRNA signature in patients with obesity with or without DM is a potential biomarker and therapeutic target in these patients.
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Affiliation(s)
- Hyoshik Kim
- Division of Nephrology, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
| | - Yun-Ui Bae
- Department of Clinical Endocrinology and Metabolism, Keimyung University School of Medicine, Daegu, Kyungsang buk do, The Republic of Korea
| | - Haekyung Lee
- Division of Nephrology, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
| | - Hyoungnae Kim
- Division of Nephrology, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
- Hyonam Kidney Laboratory, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
| | - Jin Seok Jeon
- Division of Nephrology, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
- Hyonam Kidney Laboratory, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
| | - Hyunjin Noh
- Division of Nephrology, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
- Hyonam Kidney Laboratory, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
| | - Dong Cheol Han
- Division of Nephrology, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
- Hyonam Kidney Laboratory, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
| | - Dong Won Byun
- Division of Endocrinology and Metabolism, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
| | - Sang Hyun Kim
- Department of Surgery, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
| | - Hyeong Kyu Park
- Division of Endocrinology and Metabolism, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
| | - Seongho Ryu
- Soonchunhyang Institute of Med-bio Science (SIMS), Soonchunhyang University, Asan, Chungcheongnam-do, The Republic of Korea
| | - Soon Hyo Kwon
- Division of Nephrology, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
- Hyonam Kidney Laboratory, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul, The Republic of Korea
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Substantially Altered Expression Profile of Diabetes/Cardiovascular/Cerebrovascular Disease Associated microRNAs in Children Descending from Pregnancy Complicated by Gestational Diabetes Mellitus-One of Several Possible Reasons for an Increased Cardiovascular Risk. Cells 2020; 9:cells9061557. [PMID: 32604801 PMCID: PMC7349356 DOI: 10.3390/cells9061557] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 06/19/2020] [Accepted: 06/25/2020] [Indexed: 12/14/2022] Open
Abstract
Gestational diabetes mellitus (GDM), one of the major pregnancy-related complications, characterized as a transitory form of diabetes induced by insulin resistance accompanied by a low/absent pancreatic beta-cell compensatory adaptation to the increased insulin demand, causes the acute, long-term, and transgenerational health complications. The aim of the study was to assess if alterations in gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases are present in whole peripheral blood of children aged 3-11 years descending from GDM complicated pregnancies. A substantially altered microRNA expression profile was found in children descending from GDM complicated pregnancies. Almost all microRNAs with the exception of miR-92a-3p, miR-155-5p, and miR-210-3p were upregulated. The microRNA expression profile also differed between children after normal and GDM complicated pregnancies in relation to the presence of overweight/obesity, prehypertension/hypertension, and/or valve problems and heart defects. Always, screening based on the combination of microRNAs was superior over using individual microRNAs, since at 10.0% false positive rate it was able to identify a large proportion of children with an aberrant microRNA expression profile (88.14% regardless of clinical findings, 75.41% with normal clinical findings, and 96.49% with abnormal clinical findings). In addition, the higher incidence of valve problems and heart defects was found in children with a prior exposure to GDM. The extensive file of predicted targets of all microRNAs aberrantly expressed in children descending from GDM complicated pregnancies indicates that a large group of these genes is involved in ontologies of diabetes/cardiovascular/cerebrovascular diseases. In general, children with a prior exposure to GDM are at higher risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases, and would benefit from dispensarisation as well as implementation of primary prevention strategies.
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Non-Coding RNA: Role in Gestational Diabetes Pathophysiology and Complications. Int J Mol Sci 2020; 21:ijms21114020. [PMID: 32512799 PMCID: PMC7312670 DOI: 10.3390/ijms21114020] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 05/30/2020] [Accepted: 06/02/2020] [Indexed: 12/12/2022] Open
Abstract
Gestational Diabetes Mellitus (GDM) is defined as glucose intolerance that develops in the second or third trimester of pregnancy. GDM can lead to short-term and long-term complications both in the mother and in the offspring. Diagnosing and treating this condition is therefore of great importance to avoid poor pregnancy outcomes. There is increasing interest in finding new markers with potential diagnostic, prognostic and therapeutic utility in GDM. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs, are critically involved in metabolic processes and their dysregulated expression has been reported in several pathological contexts. The aberrant expression of several circulating or placenta-related ncRNAs has been linked to insulin resistance and β-cell dysfunction, the key pathophysiological features of GDM. Furthermore, significant associations between altered ncRNA profiles and GDM-related complications, such as macrosomia or trophoblast dysfunction, have been observed. Remarkably, the deregulation of ncRNAs, which might be linked to a detrimental intrauterine environment, can lead to changes in the expression of target genes in the offspring, possibly contributing to the development of long-term GDM-related complications, such as metabolic and cardiovascular diseases. In this review, all the recent findings on ncRNAs and GDM are summarized, particularly focusing on the molecular aspects and the pathophysiological implications of this complex relationship.
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Herrera-Van Oostdam AS, Toro-Ortíz JC, López JA, Noyola DE, García-López DA, Durán-Figueroa NV, Martínez-Martínez E, Portales-Pérez DP, Salgado-Bustamante M, López-Hernández Y. Placental exosomes isolated from urine of patients with gestational diabetes exhibit a differential profile expression of microRNAs across gestation. Int J Mol Med 2020; 46:546-560. [PMID: 32626972 PMCID: PMC7307810 DOI: 10.3892/ijmm.2020.4626] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Accepted: 05/15/2020] [Indexed: 12/11/2022] Open
Abstract
Placenta‑derived exosomes play an important role in cellular communication both in the mother and the fetus. Their concentration and composition are altered in several pregnancy disorders, such as gestational diabetes mellitus (GDM). The isolation and characterization of placental exosomes from serum, plasma and tissues from patients with GDM have been previously described; however, to the best of our knowledge, to date, there is no study available on placental exosomes isolated from urine of patients with GDM. In the present study, placental exosomes were purified from urine the 1st, 2nd and 3rd trimester of gestation. Placental exosomes were characterized by transmission electron microscopy in cryogenic mode and by western blot analysis, confirming the presence of exosomal vesicles. The expression profile of five microRNAs (miR‑516‑5p, miR‑517‑3p, miR‑518‑5p, miR‑222‑3p and miR‑16‑5p) was determined by RT‑qPCR. In healthy pregnant women, the expression of the miRNAs increased across gestation, apart from miR‑516‑5p, which was not expressed at the 2nd trimester. All the miRNAs examined were downregulated in patients with GDM at the 3rd trimester of gestation. The downregulated miRNAs affected several metabolic pathways closely associated with the pathophysiology of GDM. This provides further evidence of the regulatory role of miRNAs in the GDM. This also suggests that the of urinary exosomes may be an excellent source of biomarkers and therapeutic targets.
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Affiliation(s)
- Ana Sofía Herrera-Van Oostdam
- Department of Biochemistry, Faculty of Medicine, Universidad Autónoma de San Luis Potosí, San Luis Potosí 78210, Mexico
| | - Juan Carlos Toro-Ortíz
- Division of Gynecology and Obstetrics, Hospital Central 'Dr. Ignacio Morones Prieto', San Luis Potosí 78290, Mexico
| | - Jesús Adrián López
- Laboratory of microRNAs and Cancer, Academic Unit of Biological Sciences, Universidad Autónoma de Zacatecas, Zacatecas 98068, Mexico
| | - Daniel E Noyola
- Department of Microbiology, Faculty of Medicine, Universidad Autónoma de San Luis Potosí, San Luis Potosí 78210, Mexico
| | - David Alejandro García-López
- Laboratory of Cellular Biology and Neurobiology, Academic Unit of Biological Sciences, Universidad Autónoma de Zacatecas, Zacatecas 98068, Mexico
| | - Noé Valentín Durán-Figueroa
- Interdisciplinary Professional Biotechnology Unit, Instituto Politécnico Nacional, Ciudad de Mexico 07340, Mexico
| | - Eduardo Martínez-Martínez
- Laboratory of Cell Communication and Extracellular Vesicles, Instituto Nacional de Medicina Genómica, México City 14610, Mexico
| | - Diana P Portales-Pérez
- Translational and Molecular Medicine Laboratory, Research Center for Health Sciences and Biomedicine, Universidad Autónoma de San Luis Potosí, San Luis Potosí 78290, Mexico
| | - Mariana Salgado-Bustamante
- Department of Biochemistry, Faculty of Medicine, Universidad Autónoma de San Luis Potosí, San Luis Potosí 78210, Mexico
| | - Yamilé López-Hernández
- CONACyT, Metabolomics and Proteomics Laboratory, Academic Unit of Biological Sciences, Universidad Autónoma de Zacatecas, Zacatecas 98068, Mexico
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Pheiffer C, Dias S, Rheeder P, Adam S. MicroRNA Profiling in HIV-Infected South African Women with Gestational Diabetes Mellitus. Mol Diagn Ther 2020; 23:499-505. [PMID: 31111446 DOI: 10.1007/s40291-019-00404-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Recently, we reported that the microRNAs (miRNAs) miR-20a-5p and-to a lesser extent-miR-222-3p hold potential as biomarkers for gestational diabetes mellitus (GDM) in human immunodeficiency virus (HIV)-negative South African women. METHODS In this preliminary study, we measured the expression of these miRNAs in HIV-positive women (GDM 15, non-GDM 52; median 26.0 weeks; range 16-30). RESULTS Although the same trend of decreased expression of miR-20a-5p (1.5-fold decrease) and miR-222-3p (1.4-fold decrease) was observed in sera of women with and without GDM, these differences were not statistically significant. Stratification according to antiretroviral treatment (ART) confirmed decreased expression of miR-20a-5p and miR-222-3p in ART-naïve and ART-treated women with GDM, although again this was not statistically significant. CONCLUSION Our results demonstrate that HIV infection modifies the expression of miR-20a-5p and miR-222-3p in women with GDM. Importantly, this study highlights the complexities of miRNA profiling and the need for GDM biomarker discovery in both HIV-infected and uninfected individuals, particularly in South Africa, where approximately 30% of pregnancies are complicated by HIV. Further studies to elucidate the mechanisms that underlie these miRNA differences are needed.
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Affiliation(s)
- Carmen Pheiffer
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Francie Van Zijl Drive, Tygerberg, Western Cape, 7505, South Africa. .,Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
| | - Stephanie Dias
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Francie Van Zijl Drive, Tygerberg, Western Cape, 7505, South Africa.,Department of Obstetrics and Gynecology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Paul Rheeder
- Department of Internal Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Sumaiya Adam
- Department of Obstetrics and Gynecology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
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Wang L, Zhang L. Circulating Exosomal miRNA as Diagnostic Biomarkers of Neurodegenerative Diseases. Front Mol Neurosci 2020; 13:53. [PMID: 32351363 PMCID: PMC7174585 DOI: 10.3389/fnmol.2020.00053] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 03/17/2020] [Indexed: 02/06/2023] Open
Abstract
Neurodegenerative diseases (NDDs) are a group of diseases caused by chronic and progressive degeneration of neural tissue. The main pathological manifestations are neuronal degeneration and loss in the brain and/or spinal cord. Common NDDs include Alzheimer disease (AD), Parkinson disease (PD), Huntington disease (HD), and amyotrophic lateral sclerosis (ALS). The complicated pathological characteristics and different clinical manifestations of NDDs result in a lack of sensitive and efficient diagnostic methods. In addition, no sensitive biomarkers are available to monitor the course of NDDs, predict their prognosis, and monitor the therapeutic response. Despite extensive research in recent years, analysis of amyloid β (Aβ) and α-synuclein has failed to effectively improve NDD diagnosis. Although recent studies have indicated circulating miRNAs as promising diagnostic biomarkers of NDDs, the miRNA in the peripheral circulation is susceptible to interference by other components, making circulating miRNA results less consistent. Exosomes are small membrane vesicles with a diameter of approximately 30-100 nm that transport proteins, lipids, mRNA, and miRNA. Because recent studies have shown that exosomes have a double-membrane structure that can resist ribonuclease in the blood, giving exosomal miRNA high stability and making them resistant to degradation, they may become an ideal biomarker of circulating fluids. In this review, we discuss the applicability of circulating exosomal miRNAs as biomarkers, highlight the technical aspects of exosomal miRNA analysis, and review studies that have used circulating exosomal miRNAs as candidate diagnostic biomarkers of NDDs.
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Affiliation(s)
- Lin Wang
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lijuan Zhang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
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Diabetes Mellitus and Cardiovascular Risk Assessment in Mothers with a History of Gestational Diabetes Mellitus Based on Postpartal Expression Profile of MicroRNAs Associated with Diabetes Mellitus and Cardiovascular and Cerebrovascular Diseases. Int J Mol Sci 2020; 21:ijms21072437. [PMID: 32244558 PMCID: PMC7177375 DOI: 10.3390/ijms21072437] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 03/25/2020] [Accepted: 03/30/2020] [Indexed: 02/07/2023] Open
Abstract
Mothers with a history of gestational diabetes mellitus (GDM) have an increased risk of developing diabetes in the future and a lifelong cardiovascular risk. Postpartal expression profile of cardiovascular/cerebrovascular disease associated microRNAs was assessed 3–11 years after the delivery in whole peripheral blood of young and middle-aged mothers with a prior exposure to GDM with the aim to identify a high-risk group of mothers at risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases who would benefit from implementation of early primary prevention strategies and long-term follow-up. The hypothesis of the assessment of cardiovascular risk in women was based on the knowledge that a series of microRNAs play a role in the pathogenesis of diabetes mellitus and cardiovascular/cerebrovascular diseases. Abnormal expression profile of multiple microRNAs was found in women with a prior exposure to GDM (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and-miR-574-3p). Postpartal combined screening of miR-1-3p, miR-16-5p, miR-17-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-133a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p showed the highest accuracy for the identification of mothers with a prior exposure to GDM at a higher risk of later development of cardiovascular/cerebrovascular diseases (AUC 0.900, p < 0.001, sensitivity 77.48%, specificity 93.26%, cut off >0.611270413). It was able to identify 77.48% mothers with an increased cardiovascular risk at 10.0% FPR. Any of changes in epigenome (upregulation of miR-16-5p, miR-17-5p, miR-29a-3p, and miR-195-5p) that were induced by GDM-complicated pregnancy are long-acting and may predispose mothers affected with GDM to later development of diabetes mellitus and cardiovascular/cerebrovascular diseases. In addition, novel epigenetic changes (upregulation of serious of microRNAs) appeared in a proportion of women that were exposed to GDM throughout the postpartal life. Likewise, a previous occurrence of either GH, PE, and/or FGR, as well as a previous occurrence of GDM, is associated with the upregulation of miR-1-3p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-29a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p. On the other hand, upregulation of miR-16-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-103a-3p, miR-195-5p, miR-342-3p, and miR-574-3p represents a unique feature of aberrant expression profile of women with a prior exposure to GDM. Screening of particular microRNAs may stratify a high-risk group of mothers with a history of GDM who might benefit from implementation of early primary prevention strategies.
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MicroRNA Signatures as Future Biomarkers for Diagnosis of Diabetes States. Cells 2019; 8:cells8121533. [PMID: 31795194 PMCID: PMC6953078 DOI: 10.3390/cells8121533] [Citation(s) in RCA: 106] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 11/22/2019] [Accepted: 11/24/2019] [Indexed: 12/24/2022] Open
Abstract
Diabetes results from the inability of pancreatic islets to maintain blood glucose concentrations within a normal physiological range. Clinical features are usually not observed until islets begin to fail and irreversible damage has occurred. Diabetes is generally diagnosed based on elevated glucose, which does not distinguish between type 1 and 2 diabetes. Thus, new diagnostic approaches are needed to detect different modes of diabetes before manifestation of disease. During prediabetes (pre-DM), islets undergo stress and release micro (mi) RNAs. Here, we review studies that have measured and tracked miRNAs in the blood for those with recent-onset or longstanding type 1 diabetes, obesity, pre-diabetes, type 2 diabetes, and gestational diabetes. We summarize the findings on miRNA signatures with the potential to stage progression of different modes of diabetes. Advances in identifying selective biomarker signatures may aid in early detection and classification of diabetic conditions and treatments to prevent and reverse diabetes.
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Zhu P, Liu J, Lu M, Wu G, Lin X, Cai L, Zhang X. Influence and mechanism of miR-99a suppressing development of colorectal cancer (CRC) with diabetes mellitus (DM). Onco Targets Ther 2019; 12:10311-10321. [PMID: 31819515 PMCID: PMC6885593 DOI: 10.2147/ott.s190998] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 07/18/2019] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE This study aimed to identify the changes of miRNAs in colorectal cancer (CRC) complicated with diabetes mellitus (DM) (CRC + DM) tissues and their potential effects. METHODS The changes of miRNAs in CRC + DM tissues were determined by miRNA microarray. The expression levels of miR-99a in 40 clinical specimens and 6 CRC cell lines were determined by qRT-PCR. The capacity for miR-99a to induce cell proliferation and invasion was examined with miR-99a-overexpressing HCT-116 cells. The relative mTOR mRNA and protein levels were determined by qRT-PCR and Western blotting, respectively, in HCT-116 cells transfected with miR-99a. The dual luciferase assay was performed to confirm the direct regulation of miR-99a on mTOR 3'-UTR. The HCT-116 cells were treated with 100 mg/L advanced glycation end products (AGEs); then, the mTOR expression levels were determined by qRT-PCR, Western blotting, and immunohistochemistry. RESULTS Seventeen miRNAs were found to be differentially expressed among normal tissue, CRC tissue, and CRC with DM tissue, including 15 upregulated and 2 downregulated with fold changs of more than 2 times. qRT-PCR confirmed that miR-99a was downregulated in CRC and CRC + DM tissues. In addition, miR-99a overexpression remarkably impaired CRC cell proliferation and metastasis, and negatively regulated mTOR signaling through direct binding to the 3'-UTR of mTOR. AGEs could suppress miR-99a and stimulate mTOR signaling in CRC cells. Increased mTOR was also identified in CRC with DM tissues. CONCLUSION Our findings indicate that miR-99a is a potential marker and therapeutic target of CRC complicated with DM, and that AGEs impair miR-99a-overactivated mTOR signaling in CRC with DM patients, which promotes CRC development.
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Affiliation(s)
- Peixuan Zhu
- The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Jiahao Liu
- Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Meijuan Lu
- The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Gongfa Wu
- Department of Pathology, Zengcheng District People’s Hospital of Guangzhou City, Guangzhou, People’s Republic of China
| | - Xutao Lin
- The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Longmei Cai
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Xiaona Zhang
- The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
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Gan WZ, Ramachandran V, Lim CSY, Koh RY. Omics-based biomarkers in the diagnosis of diabetes. J Basic Clin Physiol Pharmacol 2019; 31:/j/jbcpp.ahead-of-print/jbcpp-2019-0120/jbcpp-2019-0120.xml. [PMID: 31730525 DOI: 10.1515/jbcpp-2019-0120] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 10/07/2019] [Indexed: 02/06/2023]
Abstract
Diabetes mellitus (DM) is a group of metabolic diseases related to the dysfunction of insulin, causing hyperglycaemia and life-threatening complications. Current early screening and diagnostic tests for DM are based on changes in glucose levels and autoantibody detection. This review evaluates recent studies on biomarker candidates in diagnosing type 1, type 2 and gestational DM based on omics classification, whilst highlighting the relationship of these biomarkers with the development of diabetes, diagnostic accuracy, challenges and future prospects. In addition, it also focuses on possible non-invasive biomarker candidates besides common blood biomarkers.
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Affiliation(s)
- Wei Zien Gan
- Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, 57000 Kuala Lumpur, Malaysia
| | - Valsala Ramachandran
- Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, 57000 Kuala Lumpur, Malaysia
| | - Crystale Siew Ying Lim
- Department of Biotechnology, Faculty of Applied Sciences, UCSI University Kuala Lumpur, 56000 Kuala Lumpur, Malaysia
| | - Rhun Yian Koh
- Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, 57000 Kuala Lumpur, Malaysia, Phone: +60327317207
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Role of cell free microRNA-19a and microRNA-19b in gestational diabetes mellitus patients. 3 Biotech 2019; 9:406. [PMID: 31687318 DOI: 10.1007/s13205-019-1952-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 10/11/2019] [Indexed: 10/25/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes in pregnant women and it's prevalence is increasing worldwide. A total 100 cases of GDM and 100 healthy controls were included in a study and blood samples were collected in plain vials from all study participant. Difference among several variables which included BMI, glycemia, insulinaemia, HbA1c, total cholesterol, triglycerides, urinary albumin were compared between GDM cases and controls and were found to be statistically significant (p < 0.0001). Additionally, GDM cases showed 4.0 fold increase in miRNA-19a and 4.7 mean increase in miRNA-19b expression compared to healthy control individuals. A positive correlation was observed between miRNA-19a and miRNA-19b among GDM cases. However the correlation coefficient was 0.13 between miRNA-19a and miRNA-19b. This suggested that with the increase in miRNA-19a, miRNA-19b also increased. The findings of this study concludes that an increase in microRNA-19a and microRNA-19b is observed in GDM cases and could be linked with increased risk factor for worsening of the disease. MicroRNA-19a and 19b have been linked to alcoholism and smoking and could also be the factors in GDM.
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Zhou X, Xiang C, Zheng X. miR-132 serves as a diagnostic biomarker in gestational diabetes mellitus and its regulatory effect on trophoblast cell viability. Diagn Pathol 2019; 14:119. [PMID: 31653266 PMCID: PMC6814988 DOI: 10.1186/s13000-019-0899-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 10/09/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes. Strategies that improve trophoblast cell function are important methods for GDM treatment. This study aimed to investigate the expression and diagnostic potential of microRNA-132 (miR-132) in GDM patients, and further analyzed the effects of miR-132 on HTR-8/SVneo cell proliferation. METHODS Quantitative real-time PCR was applied to estimate the expression of miR-132. A receiver operating characteristics curve (ROC) analysis was performed to evaluate the diagnostic value of serum miR-132 in GDM patients. In vitro regulation of miR-132 in trophoblast cell HTR-8/SVneo was achieved by cell transfection, and the effects of miR-132 on cell proliferation were assessed using CCK-8 assay. RESULTS Expression of miR-132 was decreased in serum and placenta tissues in GDM patients compared with the healthy women. A negative correlation was found between the serum miR-132 levels and fasting blood glucose of the GDM patients. A ROC curve shown the serum miR-132 had considerable diagnostic accuracy with an area under the curve (AUC) of 0.898. High glucose (HG) treatment induced an inhibition in HTR-8/SVneo cell proliferation and the expression of miR-132. The overexpression of miR-132 in HTR-8/SVneo cells could markedly rescued the HG - induced suppressed cell proliferation. CONCLUSION All the data of this study revealed the reduced expression of miR-132 in serum and placenta tissues of GDM, and serum miR-132 serves a candidate biomarker in the diagnosis of GDM. miR-132 may act a protective role against GDM via enhancing the trophoblast cell proliferation.
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Affiliation(s)
- Xuegui Zhou
- Department of Obstetrics, Binzhou People's Hospital, No. 515, Huanghe 7 Road, Binzhou, Shandong, 256610, People's Republic of China.
| | - Cuiping Xiang
- Department of Obstetrics, Binzhou People's Hospital, No. 515, Huanghe 7 Road, Binzhou, Shandong, 256610, People's Republic of China
| | - Xiaoxia Zheng
- Department of Obstetrics, Binzhou Center Hospital, Binzhou, Shandong, 251700, People's Republic of China
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