Editors
4
Impact
Loading...
Review
21 June 2021
Emerging Role of Long Non-Coding RNAs in Diabetic Vascular Complications
Vinay Singh Tanwar
1 more and 
Rama Natarajan

Chronic metabolic disorders such as obesity and diabetes are associated with accelerated rates of macrovascular and microvascular complications, which are leading causes of morbidity and mortality worldwide. Further understanding of the underlying molecular mechanisms can aid in the development of novel drug targets and therapies to manage these disorders more effectively. Long non-coding RNAs (lncRNAs) that do not have protein-coding potential are expressed in a tissue- and species-specific manner and regulate diverse biological processes. LncRNAs regulate gene expression in cis or in trans through various mechanisms, including interaction with chromatin-modifying proteins and other regulatory proteins and via posttranscriptional mechanisms, including acting as microRNA sponges or as host genes of microRNAs. Emerging evidence suggests that major pathological factors associated with diabetes such as high glucose, free fatty acids, proinflammatory cytokines, and growth factors can dysregulate lncRNAs in inflammatory, cardiac, vascular, and renal cells leading to altered expression of key inflammatory genes and fibrotic genes associated with diabetic vascular complications. Here we review recent reports on lncRNA characterization, functions, and mechanisms of action in diabetic vascular complications and translational approaches to target them. These advances can provide new insights into the lncRNA-dependent actions and mechanisms underlying diabetic vascular complications and uncover novel lncRNA-based biomarkers and therapies to reduce disease burden and mortality.

5,800 views
45 citations
Review
11 May 2021
Epigenetics of Hepatic Insulin Resistance
Hannah Maude
1 more and 
Inês Cebola

Insulin resistance (IR) is largely recognized as a unifying feature that underlies metabolic dysfunction. Both lifestyle and genetic factors contribute to IR. Work from recent years has demonstrated that the epigenome may constitute an interface where different signals may converge to promote IR gene expression programs. Here, we review the current knowledge of the role of epigenetics in hepatic IR, focusing on the roles of DNA methylation and histone post-translational modifications. We discuss the broad epigenetic changes observed in the insulin resistant liver and its associated pathophysiological states and leverage on the wealth of ‘omics’ studies performed to discuss efforts in pinpointing specific loci that are disrupted by these changes. We envision that future studies, with increased genomic resolution and larger cohorts, will further the identification of biomarkers of early onset hepatic IR and assist the development of targeted interventions. Furthermore, there is growing evidence to suggest that persistent epigenetic marks may be acquired over prolonged exposure to disease or deleterious exposures, highlighting the need for preventative medicine and long-term lifestyle adjustments to avoid irreversible or long-term alterations in gene expression.

10,978 views
31 citations
Review
10 May 2021

Most of the sequences in the human genome do not code for proteins but generate thousands of non-coding RNAs (ncRNAs) with regulatory functions. High-throughput sequencing technologies and bioinformatic tools significantly expanded our knowledge about ncRNAs, highlighting their key role in gene regulatory networks, through their capacity to interact with coding and non-coding RNAs, DNAs and proteins. NcRNAs comprise diverse RNA species, including amongst others PIWI-interacting RNAs (piRNAs), involved in transposon silencing, and small nucleolar RNAs (snoRNAs), which participate in the modification of other RNAs such as ribosomal RNAs and transfer RNAs. Recently, a novel class of small ncRNAs generated from the cleavage of tRNAs or pre-tRNAs, called tRNA-derived small RNAs (tRFs) has been identified. tRFs have been suggested to regulate protein translation, RNA silencing and cell survival. While for other ncRNAs an implication in several pathologies is now well established, the potential involvement of piRNAs, snoRNAs and tRFs in human diseases, including diabetes, is only beginning to emerge. In this review, we summarize fundamental aspects of piRNAs, snoRNAs and tRFs biology. We discuss their biogenesis while emphasizing on novel sequencing technologies that allow ncRNA discovery and annotation. Moreover, we give an overview of genomic approaches to decrypt their mechanisms of action and to study their functional relevance. The review will provide a comprehensive landscape of the regulatory roles of these three types of ncRNAs in metabolic disorders by reporting their differential expression in endocrine pancreatic tissue as well as their contribution to diabetes incidence and diabetes-underlying conditions such as inflammation. Based on these discoveries we discuss the potential use of piRNAs, snoRNAs and tRFs as promising therapeutic targets in metabolic disorders.

7,567 views
24 citations
9,771 views
34 citations
Recommended Research Topics
27.3K
views
27
authors
4
articles
Frontiers Logo

Frontiers in Endocrinology

Revisiting Cellular Metabolism and Type 1 Diabetes
Edited by Vikash Chandra, Swetha Gopalakrishnan, Latif RACHDI
22.1K
views
38
authors
6
articles
Frontiers Logo

Frontiers in Endocrinology

Progression to Diabetes: Molecular and Cellular Mechanisms
Edited by Carlos Guillén, Adolfo Garcia-Ocana
38.9K
views
62
authors
10
articles
Frontiers Logo

Frontiers in Endocrinology

Epigenetic Mechanisms Underlying Diabetes Mellitus: Recent Advances
Edited by Shanel Raghubeer, Saarah FG Davids, Don M Matshazi, Cecil Jack Weale, Felix Chilunga, Savania Nagiah
19.4K
views
31
authors
6
articles
Frontiers Logo

Frontiers in Endocrinology

A Year in Review: Discussions in Diabetes: Molecular Mechanisms
Edited by Marcia Hiriart, Inês Cebola
106K
views
48
authors
8
articles