Regulation of Oxidative Stress by Long Non-Coding RNAs in Vascular Complications of Diabetes

Abstract

Diabetes mellitus is a well-known metabolic disorder with numerous complications, such as macrovascular diseases (e.g., coronary heart disease, diabetic cardiomyopathy, stroke, and peripheral vascular disease), microvascular diseases (e.g., diabetic nephropathy, retinopathy, and diabetic cataract), and neuropathy. Multiple contributing factors are implicated in these complications, and the accumulation of oxidative stress is one of the critical ones. Several lines of evidence have suggested that oxidative stress may induce epigenetic modifications that eventually contribute to diabetic vascular complications. As one kind of epigenetic regulator involved in various disorders, non-coding RNAs have received great attention over the past few years. Non-coding RNAs can be roughly divided into short (such as microRNAs; ~21–25 nucleotides) or long non-coding RNAs (lncRNAs; >200 nucleotides). In this review, we briefly discussed the research regarding the roles of various lncRNAs, such as MALAT1, MEG3, GAS5, SNHG16, CASC2, HOTAIR, in the development of diabetic vascular complications in response to the stimulation of oxidative stress.

Small RNA sequencing reveals snoRNAs and piRNA-019825 as novel players in diabetic kidney disease

“…GAS5-lncRNA is a snoRNA host gene which encodes a large number of snoRNAs. In addition, a number of studies have linked this lncRNA to kidney function (42)(43)(44). Interestingly, this lncRNA is also a binding partner for SNORD118 described above (45).…”

Pathomechanisms of non-coding RNAs and hub genes related to the oxidative stress in diabetic complications

“…Hence, non-coding RNAs are also interesting and attractive therapeutic targets since of their potential impact on various disease-related cellular processes. 28 Growing evidence highlighted that lncRNAs have been recognized as significant transcripts involved in oxidative stress, inflammation, cell damage, apoptosis cell death, beta-cell function, insulin resistance/insulin secretion, metabolism, etc., and are now considered potential diagnostic biomarkers. 78 Hence, lncRNAs are potentially pivotal molecules in oxidative stress, inflammation, and cell death studies.…”

“…Only a significant portion of annotated lncRNAs have been shown to play critical roles in diseases associated with oxidative stress, such as those affecting the nervous, respiratory, metabolism, and cardiovascular systems. 28 Based on the evidence, lncRNAs could be targeting ARE/Nrf2/Keap1 network and, through genetic interactions, are associated with the oxidation and antioxidation balance system. 79 As major effective lncRNAs related to oxidative stress conditions could be pointed to the MALAT1, H19, SCAL1, NEAT1, gadd7, MACC1-AS1, ODRUL, LINC01619, LINC00963, FOXD3-AS1, and BDNF-AS.…”

“…), hydroxyl radical (ÁOH), and hydrogen peroxide (H 2 O 2 ), are produced at high concentrations in response to oxidative stress, leading to damaged cells and even cell death. 28 Oxidative stress and cell death are hallmarks of diabetes and cardiovascular diseases, although managing these hallmarks may help postpone the development of diabetes and diabetic vascular complication. 14 In silico and bioinformatics analysis have revealed that the hub genes involved in cell death, cytokine production, and oxidative stress pathways could be related to T2D (Figures 1-3).…”

Regulation of Oxidative Stress by Long Non-coding RNAs in Central Nervous System Disorders

“…LncRNAs are involved in the regulation of cell proliferation, differentiation, the cell cycle, and apoptosis at the transcriptional, post-transcriptional, and epigenetic levels. Furthermore, a few annotated lncRNAs play an important role in oxidative stress-related diseases and CNS disorders ( Chu et al, 2022 ). For instance, elevated levels of the lncRNA rhabdomyosarcoma 2 related transcript (RMST) augment AIS by reducing microRNA (miR)-221-3p-mediated regulation of phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) and activating the transforming growth factor-β (TGF-β) pathway ( Li et al, 2022 ).…”