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ncRNA
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Non-Coding RNA and Diabetes
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Non-Coding RNA and Diabetes

A special issue of Non-Coding RNA (ISSN 2311-553X).

Deadline for manuscript submissions: closed (30 September 2018) | Viewed by 32575

Special Issue Editors

Prof. Dr. Flemming Pociot

E-Mail Website
Guest Editor
Steno Diabetes Center Copenhagen, Gentofte, Denmark
Interests: Type 1 Diabetes; epigenetics; β-cell function; genetic epidemiology; systems biology; non-coding RNA
Dr. Aashiq H. Mirza

E-Mail Website
Guest Editor
Weill Cornell Medical College, New York, NY, USA
Interests: RNA biology; cancer cell biology; long non-coding RNAs; transcriptomics
Dr. Simranjeet Kaur

E-Mail Website
Guest Editor
Translational Type 1 Diabetes Research, Steno Diabetes Center Copenhagen, 2739 Herlev, Denmark
Interests: human genomics; genetics; chromatin; 3D genome organization; epigenetics; non-coding RNAs; autoimmune diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Diabetes mellitus is a heterogeneous collection of disorders associated with abnormal glucose homeostasis, pancreatic β-cell death and accelerated rates of micro- and macrovascular complications that increase morbidity and mortality. The role of non-coding RNAs (ncRNAs) in pathogenesis of Type 1 and Type 2 diabetes and related complications has only recently been recognized. Growing evidence implicates microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the etiology of diabetes and related renal and retinal microvascular complications. Small ncRNAs including miRNAs and piwi-interacting RNAs (piRNAs) have been associated with disease progression and β-cell function. Hundreds of novel islet-specific lncRNAs have been identified and a few associated with β-cell failure, insulin secretion and increased β-cell apoptosis. There is a huge potential for ncRNAs to serve as therapeutic targets for drug development and diagnostic markers for clinical applications in the management of diabetes. In this Special Issue of “Non-Coding RNA and Diabetes”, we invite experts in the field of diabetes to submit original research, methods, and review manuscripts on the latest advances in the role of ncRNAs in relation to Type 1 and Type 2 diabetes and related complications.

Prof. Dr. Flemming Pociot
Dr. Aashiq H. Mirza
Dr. Simranjeet Kaur
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Non-Coding RNA is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Non-coding RNAs
  • Type 1 diabetes
  • Type 2 diabetes
  • Diabetic complications
  • Long non-coding RNAs
  • microRNAs
  • pancreatic islets
  • microvascular dysfunction
  • renal and retinal complications

Published Papers (6 papers)

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Research

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12 pages, 1457 KiB  
Article
Rapid Generation of Long Noncoding RNA Knockout Mice Using CRISPR/Cas9 Technology
by Nils R. Hansmeier, Pia J. M. Widdershooven, Sajjad Khani and Jan-Wilhelm Kornfeld
Non-Coding RNA 2019, 5(1), 12; https://doi.org/10.3390/ncrna5010012 - 23 Jan 2019
Cited by 11 | Viewed by 6400
Abstract
In recent years, long noncoding RNAs (lncRNAs) have emerged as multifaceted regulators of gene expression, controlling key developmental and disease pathogenesis processes. However, due to the paucity of lncRNA loss-of-function mouse models, key questions regarding the involvement of lncRNAs in organism homeostasis and [...] Read more.
In recent years, long noncoding RNAs (lncRNAs) have emerged as multifaceted regulators of gene expression, controlling key developmental and disease pathogenesis processes. However, due to the paucity of lncRNA loss-of-function mouse models, key questions regarding the involvement of lncRNAs in organism homeostasis and (patho)-physiology remain difficult to address experimentally in vivo. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 platform provides a powerful genome-editing tool and has been successfully applied across model organisms to facilitate targeted genetic mutations, including Caenorhabditis elegans, Drosophila melanogaster, Danio rerio and Mus musculus. However, just a few lncRNA-deficient mouse lines have been created using CRISPR/Cas9-mediated genome engineering, presumably due to the need for lncRNA-specific gene targeting strategies considering the absence of open-reading frames in these loci. Here, we describe a step-wise procedure for the generation and validation of lncRNA loss-of-function mouse models using CRISPR/Cas9-mediated genome engineering. In a proof-of-principle approach, we generated mice deficient for the liver-enriched lncRNA Gm15441, which we found downregulated during development of metabolic disease and induced during the feeding/fasting transition. Further, we discuss guidelines for the selection of lncRNA targets and provide protocols for in vitro single guide RNA (sgRNA) validation, assessment of in vivo gene-targeting efficiency and knockout confirmation. The procedure from target selection to validation of lncRNA knockout mouse lines can be completed in 18–20 weeks, of which <10 days hands-on working time is required. Full article
(This article belongs to the Special Issue Non-Coding RNA and Diabetes)
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20 pages, 2303 KiB  
Article
Cell Type-Selective Expression of Circular RNAs in Human Pancreatic Islets
by Simranjeet Kaur, Aashiq H. Mirza and Flemming Pociot
Non-Coding RNA 2018, 4(4), 38; https://doi.org/10.3390/ncrna4040038 - 27 Nov 2018
Cited by 28 | Viewed by 3919
Abstract
Understanding distinct cell-type specific gene expression in human pancreatic islets is important for developing islet regeneration strategies and therapies to improve β-cell function in type 1 diabetes (T1D). While numerous transcriptome-wide studies on human islet cell-types have focused on protein-coding genes, the non-coding [...] Read more.
Understanding distinct cell-type specific gene expression in human pancreatic islets is important for developing islet regeneration strategies and therapies to improve β-cell function in type 1 diabetes (T1D). While numerous transcriptome-wide studies on human islet cell-types have focused on protein-coding genes, the non-coding repertoire, such as long non-coding RNA, including circular RNAs, remains mostly unexplored. Here, we explored transcriptional landscape of human α-, β-, and exocrine cells from published total RNA sequencing (RNA-seq) datasets to identify circular RNAs (circRNAs). Our analysis revealed that circRNAs are highly abundant in both α- and β-cells. We identified 10,830 high-confidence circRNAs expressed in human α-, β-, and exocrine cells. The most highly expressed candidates were MAN1A2, RMST, and HIPK3 across the three cell-types. Alternate circular isoforms were observed for circRNAs in the three cell-types, indicative of potential distinct functions. Highly selective α- and β-cell circRNAs were identified, which is suggestive of their potential role in regulating β-cell function. Full article
(This article belongs to the Special Issue Non-Coding RNA and Diabetes)
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17 pages, 863 KiB  
Article
Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism
by Giuseppina E. Grieco, Dorica Cataldo, Elena Ceccarelli, Laura Nigi, Giovanna Catalano, Noemi Brusco, Francesca Mancarella, Giuliana Ventriglia, Cecilia Fondelli, Elisa Guarino, Isabella Crisci, Guido Sebastiani and Francesco Dotta
Non-Coding RNA 2018, 4(4), 37; https://doi.org/10.3390/ncrna4040037 - 27 Nov 2018
Cited by 37 | Viewed by 3588
Abstract
Type 1 diabetes (T1D) is characterized by bone loss and altered bone remodeling, resulting into reduction of bone mineral density (BMD) and increased risk of fractures. Identification of specific biomarkers and/or causative factors of diabetic bone fragility is of fundamental importance for an [...] Read more.
Type 1 diabetes (T1D) is characterized by bone loss and altered bone remodeling, resulting into reduction of bone mineral density (BMD) and increased risk of fractures. Identification of specific biomarkers and/or causative factors of diabetic bone fragility is of fundamental importance for an early detection of such alterations and to envisage appropriate therapeutic interventions. MicroRNAs (miRNAs) are small non-coding RNAs which negatively regulate genes expression. Of note, miRNAs can be secreted in biological fluids through their association with different cellular components and, in such context, they may represent both candidate biomarkers and/or mediators of bone metabolism alterations. Here, we aimed at identifying miRNAs differentially expressed in serum of T1D patients and potentially involved in bone loss in type 1 diabetes. We selected six miRNAs previously associated with T1D and bone metabolism: miR-21; miR-24; miR-27a; miR-148a; miR-214; and miR-375. Selected miRNAs were analyzed in sera of 15 T1D patients (age: 33.57 ± 8.17; BMI: 21.4 ± 1.65) and 14 non-diabetic subjects (age: 31.7 ± 8.2; BMI: 24.6 ± 4.34). Calcium, osteocalcin, parathormone (PTH), bone ALkaline Phoshatase (bALP), and Vitamin D (VitD) as well as main parameters of bone health were measured in each patient. We observed an increased expression of miR-148a (p = 0.012) and miR-21-5p (p = 0.034) in sera of T1D patients vs. non-diabetic subjects. The correlation analysis between miRNAs expression and the main parameters of bone metabolism, showed a correlation between miR-148a and Bone Mineral Density (BMD) total body (TB) values (p = 0.042) and PTH circulating levels (p = 0.033) and the association of miR-21-5p to Bone Mineral Content-Femur (BMC-FEM). Finally, miR-148a and miR-21-5p target genes prediction analysis revealed several factors involved in bone development and remodeling, such as MAFB, WNT1, TGFB2, STAT3, or PDCD4, and the co-modulation of common pathways involved in bone homeostasis thus potentially assigning a role to both miR-148a and miR-21-5p in bone metabolism alterations. In conclusion, these results lead us to hypothesize a potential role for miR-148a and miR-21-5p in bone remodeling, thus representing potential biomarkers of bone fragility in T1D. Full article
(This article belongs to the Special Issue Non-Coding RNA and Diabetes)
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11 pages, 652 KiB  
Article
Influence of Disease Duration on Circulating Levels of miRNAs in Children and Adolescents with New Onset Type 1 Diabetes
by Nasim Samandari, Aashiq H. Mirza, Simranjeet Kaur, Philip Hougaard, Lotte B. Nielsen, Siri Fredheim, Henrik B. Mortensen and Flemming Pociot
Non-Coding RNA 2018, 4(4), 35; https://doi.org/10.3390/ncrna4040035 - 21 Nov 2018
Cited by 23 | Viewed by 3243
Abstract
Circulating microRNAs (miRNAs) have been implicated in several pathologies including type 1 diabetes. In the present study, we aimed to identify circulating miRNAs affected by disease duration in children with recent onset type 1 diabetes. Forty children and adolescents from the Danish Remission [...] Read more.
Circulating microRNAs (miRNAs) have been implicated in several pathologies including type 1 diabetes. In the present study, we aimed to identify circulating miRNAs affected by disease duration in children with recent onset type 1 diabetes. Forty children and adolescents from the Danish Remission Phase Cohort were followed with blood samples drawn at 1, 3, 6, 12, and 60 months after diagnosis. Pancreatic autoantibodies were measured at each visit. Cytokines were measured only the first year. miRNA expression profiling was performed by RT-qPCR. The effect of disease duration was analyzed by mixed models for repeated measurements adjusted for sex and age. Eight miRNAs (hsa-miR-10b-5p, hsa-miR-17-5p, hsa-miR-30e-5p, hsa-miR-93-5p, hsa-miR-99a-5p, hsa-miR-125b-5p, hsa-miR-423-3p, and hsa-miR-497-5p) were found to significantly change in expression (adjusted p-value < 0.05) with disease progression. Three pancreatic autoantibodies, ICA, IA-2A, and GAD65A, and four cytokines, IL-4, IL-10, IL-21, and IL-22, were associated with the miRNAs at different time points. Pathway analysis revealed associations with various immune-mediated signaling pathways. Eight miRNAs that were involved in immunological pathways changed expression levels during the first five years after diagnosis and were associated with variations in cytokine and pancreatic antibodies, suggesting a possible effect on the immunological processes in the early phase of the disease. Full article
(This article belongs to the Special Issue Non-Coding RNA and Diabetes)
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Review

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25 pages, 2042 KiB  
Review
Non-Coding RNA in Pancreas and β-Cell Development
by Wilson K. M. Wong, Anja E. Sørensen, Mugdha V. Joglekar, Anand A. Hardikar and Louise T. Dalgaard
Non-Coding RNA 2018, 4(4), 41; https://doi.org/10.3390/ncrna4040041 - 13 Dec 2018
Cited by 40 | Viewed by 6737
Abstract
In this review, we provide an overview of the current knowledge on the role of different classes of non-coding RNAs for islet and β-cell development, maturation and function. MicroRNAs (miRNAs), a prominent class of small RNAs, have been investigated for more than two [...] Read more.
In this review, we provide an overview of the current knowledge on the role of different classes of non-coding RNAs for islet and β-cell development, maturation and function. MicroRNAs (miRNAs), a prominent class of small RNAs, have been investigated for more than two decades and patterns of the roles of different miRNAs in pancreatic fetal development, islet and β-cell maturation and function are now emerging. Specific miRNAs are dynamically regulated throughout the period of pancreas development, during islet and β-cell differentiation as well as in the perinatal period, where a burst of β-cell replication takes place. The role of long non-coding RNAs (lncRNA) in islet and β-cells is less investigated than for miRNAs, but knowledge is increasing rapidly. The advent of ultra-deep RNA sequencing has enabled the identification of highly islet- or β-cell-selective lncRNA transcripts expressed at low levels. Their roles in islet cells are currently only characterized for a few of these lncRNAs, and these are often associated with β-cell super-enhancers and regulate neighboring gene activity. Moreover, ncRNAs present in imprinted regions are involved in pancreas development and β-cell function. Altogether, these observations support significant and important actions of ncRNAs in β-cell development and function. Full article
(This article belongs to the Special Issue Non-Coding RNA and Diabetes)
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25 pages, 312 KiB  
Review
Diabetes in Pregnancy and MicroRNAs: Promises and Limitations in Their Clinical Application
by Adriana Ibarra, Begoña Vega-Guedes, Yeray Brito-Casillas and Ana M. Wägner
Non-Coding RNA 2018, 4(4), 32; https://doi.org/10.3390/ncrna4040032 - 12 Nov 2018
Cited by 34 | Viewed by 7855
Abstract
Maternal diabetes is associated with an increased risk of complications for the mother and her offspring. The latter have an increased risk of foetal macrosomia, hypoglycaemia, respiratory distress syndrome, preterm delivery, malformations and mortality but also of life-long development of obesity and diabetes. [...] Read more.
Maternal diabetes is associated with an increased risk of complications for the mother and her offspring. The latter have an increased risk of foetal macrosomia, hypoglycaemia, respiratory distress syndrome, preterm delivery, malformations and mortality but also of life-long development of obesity and diabetes. Epigenetics have been proposed as an explanation for this long-term risk, and microRNAs (miRNAs) may play a role, both in short- and long-term outcomes. Gestation is associated with increasing maternal insulin resistance, as well as β-cell expansion, to account for the increased insulin needs and studies performed in pregnant rats support a role of miRNAs in this expansion. Furthermore, several miRNAs are involved in pancreatic embryonic development. On the other hand, maternal diabetes is associated with changes in miRNA both in maternal and in foetal tissues. This review aims to summarise the existing knowledge on miRNAs in gestational and pre-gestational diabetes, both as diagnostic biomarkers and as mechanistic players, in the development of gestational diabetes itself and also of short- and long-term complications for the mother and her offspring. Full article
(This article belongs to the Special Issue Non-Coding RNA and Diabetes)
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