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Non-coding RNA and Diabetes 2.0
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Non-coding RNA and Diabetes 2.0

A special issue of Non-Coding RNA (ISSN 2311-553X). This special issue belongs to the section "Detection and Biomarkers of Non-Coding RNA".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 13591

Special Issue Editor

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.

Dr. Simranjeet Kaur
Guest Editor

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.

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Published Papers (5 papers)

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12 pages, 1639 KiB  
Article
Downregulation of Exosomal hsa-miR-551b-3p in Obesity and Its Link to Type 2 Diabetes Mellitus
by Kseniia V. Dracheva, Irina A. Pobozheva, Kristina A. Anisimova, Stanislav G. Balandov, Maria N. Grunina, Zarina M. Hamid, Dmitriy I. Vasilevsky, Sofya N. Pchelina and Valentina V. Miroshnikova
Non-Coding RNA 2023, 9(6), 67; https://doi.org/10.3390/ncrna9060067 - 2 Nov 2023
Cited by 4 | Viewed by 1912
Abstract
Obesity is a significant risk factor for the development of type 2 diabetes mellitus (T2DM). Adipose tissue dysfunction can affect the pool of circulating exosomal miRNAs, driving concomitant disease in obesity. These exosomal miRNAs can reflect adipose tissue functionality, thus serving as prognostic [...] Read more.
Obesity is a significant risk factor for the development of type 2 diabetes mellitus (T2DM). Adipose tissue dysfunction can affect the pool of circulating exosomal miRNAs, driving concomitant disease in obesity. These exosomal miRNAs can reflect adipose tissue functionality, thus serving as prognostic biomarkers for disease monitoring in case of T2DM. In the present study, we conducted NanoString microRNA profiling of extracellular vesicles (EVs) secreted by adipose tissue of obese patients (body mass index (BMI) > 35) without T2DM and nonobese individuals (BMI < 30) as a control group. Functional and pathway enrichment analysis showed that miRNAs associated with obesity in this study were implicated in insulin signaling and insulin resistance biological pathways. Further, these microRNAs were screened in serum EVs in the following groups: (1) obese patients with T2DM, (2) obese patients without T2DM, and (3) nonobese individuals as a control group. has-miR-551b-3p was shown to be downregulated in adipose tissue EVs, as well as in serum EVs, of patients with obesity without T2DM. At the same time, the serum exosomal hsa-miR-551b-3p content was significantly higher in obese patients with T2DM when compared with obese patients without T2DM and may be a potential biomarker of T2DM development in obesity. Full article
(This article belongs to the Special Issue Non-coding RNA and Diabetes 2.0)
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14 pages, 2140 KiB  
Article
Altered Expression of Vitamin D Metabolism Genes and Circulating MicroRNAs in PBMCs of Patients with Type 1 Diabetes: Their Association with Vitamin D Status and Ongoing Islet Autoimmunity
by Hakeemah Al-Nakhle, Ihsan Mohsen, Bashir Elnaem, Abdullah Alharbi, Ibtisam Alnakhli, Shareefa Almoarfi and Jameela Fallatah
Non-Coding RNA 2023, 9(5), 60; https://doi.org/10.3390/ncrna9050060 - 7 Oct 2023
Cited by 3 | Viewed by 2085
Abstract
Background: The immunomodulatory role of 1,25-Dihydroxy vitamin D3 (1,25(OH)2D3) is exerted through its interaction with the vitamin D receptor (VDR) present on pancreatic and immune cells. While a deficiency in vitamin D has been linked to Type 1 Diabetes Mellitus (T1DM), the exact [...] Read more.
Background: The immunomodulatory role of 1,25-Dihydroxy vitamin D3 (1,25(OH)2D3) is exerted through its interaction with the vitamin D receptor (VDR) present on pancreatic and immune cells. While a deficiency in vitamin D has been linked to Type 1 Diabetes Mellitus (T1DM), the exact molecular mechanism driving this down-regulation in T1DM is yet to be fully understood. This study aimed to decipher differences in the expression of genes associated with vitamin D metabolism in T1DM patients and to ascertain if there is a correlation between serum 1,25(OH)2D3 levels and the expression of these genes. We also sought to understand the influence of specific microRNAs (miRNAs) on the expression of vitamin D metabolism genes in peripheral blood mononuclear cells (PBMCs) of T1DM patients. Furthermore, the study delved into the potential implications of altered vitamin D metabolism genes and miRNAs on autoimmune processes. Methods: Utilizing real-time PCR, we assessed the expression profiles of genes encoding for 1-hydroxylases (CYP27B1) and 24-hydroxylases (CYP24A1), as well as related miRNAs, in PBMCs from 30 T1DM patients and 23 healthy controls. ELISA tests facilitated the measurement of 1,25(OH)2D3, GAD65, and IA-2 levels. Results: Our findings showcased downregulated CYP27B1 mRNA levels, while CYP24A1 expression remained stable compared to healthy subjects (CYP27B1, p = 0.0005; CYP24A1, p = 0.205, respectively). In T1DM patients, the levels of has-miR-216b-5p were found to be increased, while the levels of has-miR-21-5p were decreased in comparison to the control group. Notably, no correlation was identified between the expression of CYP27B1 in T1DM patients and the levels of has-miR-216b-5p, has-miR-21-5p, and 1,25(OH)2D3. A significant negative correlation was identified between CYP27B1 mRNA levels in PBMCs of T1DM and IA2, but not with GAD65. Conclusions: The study highlights there were reduced levels of both CYP27B1 mRNA and has-miR-21-5p, along with elevated levels of has-miR-216b-5p in the PBMCs of T1DM. However, the absence of a correlation between the expression of CYP27B1, levels of has-miR-216b-5p, and the status of 1,25(OH)2D3 suggests the possible existence of other regulatory mechanisms. Additionally, the inverse relationship between IA2 autoantibodies and CYP27B1 expression in T1DM patients indicates a potential connection between this gene and the autoimmune processes inherent in T1DM. Full article
(This article belongs to the Special Issue Non-coding RNA and Diabetes 2.0)
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20 pages, 2819 KiB  
Article
T2DB: A Web Database for Long Non-Coding RNA Genes in Type II Diabetes
by Rebecca Distefano, Mirolyuba Ilieva, Jens Hedelund Madsen, Hideshi Ishii, Masanori Aikawa, Sarah Rennie and Shizuka Uchida
Non-Coding RNA 2023, 9(3), 30; https://doi.org/10.3390/ncrna9030030 - 8 May 2023
Cited by 5 | Viewed by 3612
Abstract
Type II diabetes (T2D) is a growing health problem worldwide due to increased levels of obesity and can lead to other life-threatening diseases, such as cardiovascular and kidney diseases. As the number of individuals diagnosed with T2D rises, there is an urgent need [...] Read more.
Type II diabetes (T2D) is a growing health problem worldwide due to increased levels of obesity and can lead to other life-threatening diseases, such as cardiovascular and kidney diseases. As the number of individuals diagnosed with T2D rises, there is an urgent need to understand the pathogenesis of the disease in order to prevent further harm to the body caused by elevated blood glucose levels. Recent advances in long non-coding RNA (lncRNA) research may provide insights into the pathogenesis of T2D. Although lncRNAs can be readily detected in RNA sequencing (RNA-seq) data, most published datasets of T2D patients compared to healthy donors focus only on protein-coding genes, leaving lncRNAs to be undiscovered and understudied. To address this knowledge gap, we performed a secondary analysis of published RNA-seq data of T2D patients and of patients with related health complications to systematically analyze the expression changes of lncRNA genes in relation to the protein-coding genes. Since immune cells play important roles in T2D, we conducted loss-of-function experiments to provide functional data on the T2D-related lncRNA USP30-AS1, using an in vitro model of pro-inflammatory macrophage activation. To facilitate lncRNA research in T2D, we developed a web application, T2DB, to provide a one-stop-shop for expression profiling of protein-coding and lncRNA genes in T2D patients compared to healthy donors or subjects without T2D. Full article
(This article belongs to the Special Issue Non-coding RNA and Diabetes 2.0)
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19 pages, 3179 KiB  
Article
Pro-Inflammatory Cytokines Promote the Transcription of Circular RNAs in Human Pancreatic β Cells
by Simranjeet Kaur, Caroline Frørup, Aashiq H. Mirza, Tina Fløyel, Reza Yarani, Maikel L. Colli, Jesper Johannesen, Joachim Størling, Decio L. Eizirik and Flemming Pociot
Non-Coding RNA 2022, 8(5), 69; https://doi.org/10.3390/ncrna8050069 - 12 Oct 2022
Cited by 1 | Viewed by 2965
Abstract
Circular RNAs (circRNAs) have recently been implicated in impaired β-cell function in diabetes. Using microarray-based profiling of circRNAs in human EndoC-βH1 cells treated with pro-inflammatory cytokines, this study aimed to investigate the expression and possible regulatory roles of circRNAs in human β cells. [...] Read more.
Circular RNAs (circRNAs) have recently been implicated in impaired β-cell function in diabetes. Using microarray-based profiling of circRNAs in human EndoC-βH1 cells treated with pro-inflammatory cytokines, this study aimed to investigate the expression and possible regulatory roles of circRNAs in human β cells. We identified ~5000 β-cell-expressed circRNAs, of which 84 were differentially expressed (DE) after cytokine exposure. Pathway analysis of the host genes of the DE circRNAs revealed the enrichment of cytokine signaling pathways, indicative of circRNA transcription from inflammatory genes in response to cytokines. Multiple binding sites for β-cell-enriched microRNAs and RNA-binding proteins were observed for the highly upregulated circRNAs, supporting their function as ‘sponges’ or ‘decoys’. We also present evidence for circRNA sequence conservation in multiple species, the presence of cytokine-induced regulatory elements, and putative protein-coding potential for the DE circRNAs. This study highlights the complex regulatory potential of circRNAs, which may play a crucial role during immune-mediated β-cell destruction in type 1 diabetes. Full article
(This article belongs to the Special Issue Non-coding RNA and Diabetes 2.0)
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18 pages, 3529 KiB  
Systematic Review
Extracellular microRNAs in Relation to Weight Loss—A Systematic Review and Meta-Analysis
by Camilla H. B. Veie, Isabella M. T. Nielsen, Nanna L. S. Frisk and Louise T. Dalgaard
Non-Coding RNA 2023, 9(5), 53; https://doi.org/10.3390/ncrna9050053 - 14 Sep 2023
Cited by 2 | Viewed by 1882
Abstract
Obesity is an important risk factor for cardiovascular disease and type 2 diabetes mellitus. Even a modest weight loss of 5–15% improves metabolic health, but circulating markers to indicate weight loss efficiency are lacking. MicroRNAs, small non-coding post-transcriptional regulators of gene expression, are [...] Read more.
Obesity is an important risk factor for cardiovascular disease and type 2 diabetes mellitus. Even a modest weight loss of 5–15% improves metabolic health, but circulating markers to indicate weight loss efficiency are lacking. MicroRNAs, small non-coding post-transcriptional regulators of gene expression, are secreted from tissues into the circulation and may be potential biomarkers for metabolic health. However, it is not known which specific microRNA species are reproducibly changed in levels by weight loss. In this study, we performed a systematic review and meta-analysis to investigate the microRNAs associated with weight loss by comparing baseline to follow-up levels following intervention-driven weight loss. This systematic review was performed according to the PRISMA guidelines with searches in PubMed and SCOPUS. The primary search resulted in a total of 697 articles, which were screened according to the prior established inclusion and exclusion criteria. Following the screening of articles, the review was based on the inclusion of 27 full-text articles, which were evaluated for quality and the risk of bias. We performed systematic data extraction, whereafter the relative values for miRNAs were calculated. A meta-analysis was performed for the miRNA species investigated in three or more studies: miR-26a, miR-126, and miR-223 were overall significantly increased following weight loss, while miR-142 was significantly decreased after weight loss. miR-221, miR-140, miR-122, and miR-146 were not significantly changed by intervention-driven weight loss. These results indicate that few miRNAs are significantly changed during weight loss. Full article
(This article belongs to the Special Issue Non-coding RNA and Diabetes 2.0)
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