Oxidative Stress Associated Non-coding RNAs in Pathogenesis of Urologic Cancers; Prognostic and Therapeutic Importance

Type 2 diabetes is a chronic disease widespread throughout the world, with significant human, social, and economic costs. Its multifactorial etiology leads to persistent hyperglycemia, impaired carbohydrate and fat metabolism, chronic inflammation, and defects in insulin secretion or insulin action, or both. Emerging evidence reveals that oxidative stress has a critical role in the development of type 2 diabetes. Overproduction of reactive oxygen species can promote an imbalance between the production and neutralization of antioxidant defence systems, thus favoring lipid accumulation, cellular stress, and the activation of cytosolic signaling pathways, and inducing β-cell dysfunction, insulin resistance, and tissue inflammation. Over the last few years, microRNAs (miRNAs) have attracted growing attention as important mediators of diverse aspects of oxidative stress. These small endogenous non-coding RNAs of 19–24 nucleotides act as negative regulators of gene expression, including the modulation of redox signaling pathways. The present review aims to provide an overview of the current knowledge concerning the molecular crosstalk that takes place between oxidative stress and microRNAs in the physiopathology of type 2 diabetes, with a special emphasis on its potential as a therapeutic target.

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Long Non-coding RNA XIST Attenuates Diabetic Peripheral Neuropathy by Inducing Autophagy Through MicroRNA-30d-5p/sirtuin1 Axis

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.655157 ◽

2021 ◽

Vol 8 ◽

Author(s):

Bei-Yan Liu ◽

Lin Li ◽

Li-Wei Bai ◽

Chang-Shui Xu

Keyword(s):

Oxidative Stress ◽

Peripheral Neuropathy ◽

Schwann Cells ◽

Diabetic Peripheral Neuropathy ◽

Beclin 1 ◽

Diabetic Mice ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Long Non Coding Rna

Diabetic peripheral neuropathy (DPN) is a prevalent diabetes mellitus (Feldman et al., 2017) complication and the primary reason for amputation. Meanwhile, long non-coding RNAs (lncRNAs) are a type of regulatory non-coding RNAs (ncRNAs) that broadly participate in DPN development. However, the correlation of lncRNA X-inactive specific transcript (XIST) with DPN remains unclear. In this study, we were interested in the role of XIST in the modulation of DPN progression. Significantly, our data showed that the expression of XIST and sirtuin1 (SIRT1) was inhibited, and the expression of microRNA-30d-5p (miR-30d-5p) was enhanced in the trigeminal sensory neurons of the diabetic mice compared with the normal mice. The levels of LC3II and Beclin-1 were inhibited in the diabetic mice. The treatment of high glucose (HG) reduced the XIST expression in Schwann cells. The apoptosis of Schwann cells was enhanced in the HG-treated cells, but the overexpression of XIST could block the effect in the cells. Moreover, the levels of LC3II and Beclin-1 were reduced in the HG-treated Schwann cells, while the overexpression of XIST was able to reverse this effect. The HG treatment promoted the production of oxidative stress, while the XIST overexpression could attenuate this result in the Schwann cells. Mechanically, XIST was able to sponge miR-30d-5p and miR-30d-5p-targeted SIRT1 in the Schwann cells. MiR-30d-5p inhibited autophagy and promoted oxidative stress in the HG-treated Schwann cells, and SIRT1 presented a reversed effect. MiR-30d-5p mimic or SIRT1 depletion could reverse XIST overexpression-mediated apoptosis and autophagy of the Schwann cells. Thus, we concluded that XIST attenuated DPN by inducing autophagy through miR-30d-5p/SIRT1 axis. XIST and miR-30d-5p may be applied as the potential targets for DPN therapy.

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The Role of MicroRNAs in Diabetes-Related Oxidative Stress

International Journal of Molecular Sciences ◽

10.3390/ijms20215423 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5423 ◽

Cited By ~ 3

Author(s):

Mirza Muhammad Fahd Qadir ◽

Dagmar Klein ◽

Silvia Álvarez-Cubela ◽

Juan Domínguez-Bendala ◽

Ricardo Luis Pastori

Keyword(s):

Oxidative Stress ◽

Target Gene ◽

Cellular Stress ◽

Cellular Damage ◽

Oxygen Species ◽

Non Coding Rnas ◽

And Oxidative Stress

Cellular stress, combined with dysfunctional, inadequate mitochondrial phosphorylation, produces an excessive amount of reactive oxygen species (ROS) and an increased level of ROS in cells, which leads to oxidation and subsequent cellular damage. Because of its cell damaging action, an association between anomalous ROS production and disease such as Type 1 (T1D) and Type 2 (T2D) diabetes, as well as their complications, has been well established. However, there is a lack of understanding about genome-driven responses to ROS-mediated cellular stress. Over the last decade, multiple studies have suggested a link between oxidative stress and microRNAs (miRNAs). The miRNAs are small non-coding RNAs that mostly suppress expression of the target gene by interaction with its 3’untranslated region (3′UTR). In this paper, we review the recent progress in the field, focusing on the association between miRNAs and oxidative stress during the progression of diabetes.

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Non-coding RNAs are involved in the response to oxidative stress

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2020.110228 ◽

2020 ◽

Vol 127 ◽

pp. 110228 ◽

Cited By ~ 4

Author(s):

Soudeh Ghafouri-Fard ◽

Hamed Shoorei ◽

Mohammad Taheri

Keyword(s):

Oxidative Stress ◽

Non Coding Rnas

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Insights into the Role of MicroRNAs in the Onset and Development of Diabetic Neuropathy

International Journal of Molecular Sciences ◽

10.3390/ijms20184627 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4627 ◽

Cited By ~ 5

Author(s):

Raffaele Simeoli ◽

Alessandra Fierabracci

Keyword(s):

Oxidative Stress ◽

Diabetic Neuropathy ◽

Peripheral Nerves ◽

Recent Literature ◽

Polyol Pathway ◽

Cytokine Release ◽

Chronic Hyperglycemia ◽

Pathway Activation ◽

Non Coding Rnas

Diabetic neuropathy is a serious complication of chronic hyperglycemia in diabetes patients. This complication can involve both peripheral sensorimotor and autonomic nervous system. The precise nature of injury to the peripheral nerves mediated by chronic hyperglycemia is unknown; however, several mechanisms have been proposed including polyol pathway activation, enhanced glycation of proteins and lipids, increased oxidative stress, and cytokine release in the site of injury. MicroRNAs (miRNAs) are small non-coding RNAs that mediate RNA interference by post-transcriptionally modulating gene expression and protein synthesis. Therefore, they have been implicated in several developmental, physiological, and pathophysiological processes where they modulate the expression of different proteins. Recently, miRNAs gained an increasing attention also for their role as diagnostic test in many diseases due to their stability in serum and their easy detection. Furthermore, recent studies suggest that miRNAs may be involved in diabetic neuropathy although their role in the onset and the development of this complication is not fully understood. In this review, we discuss the most recent literature providing evidence for miRNAs role in diabetic neuropathy opening new pathways to improve both early diagnosis and treatment of this complication.

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The Role of Non-coding RNAs in Diabetic Nephropathy-Related Oxidative Stress

Frontiers in Medicine ◽

10.3389/fmed.2021.626423 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xiaoyun He ◽

Gaoyan Kuang ◽

Yi Zuo ◽

Shuangxi Li ◽

Suxian Zhou ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Interstitial Fibrosis ◽

Rna Molecules ◽

Non Coding Rnas ◽

Molecular Therapeutic ◽

Stage Renal Disease ◽

End Stage ◽

Molecular Therapeutic Targets

Diabetic nephropathy (DN) is one of the main complications of diabetes and the main cause of diabetic end-stage renal disease, which is often fatal. DN is usually characterized by progressive renal interstitial fibrosis, which is closely related to the excessive accumulation of extracellular matrix and oxidative stress. Non-coding RNAs (ncRNAs) are RNA molecules expressed in eukaryotic cells that are not translated into proteins. They are widely involved in the regulation of biological processes, such as, chromatin remodeling, transcription, post-transcriptional modification, and signal transduction. Recent studies have shown that ncRNAs play an important role in the occurrence and development of DN and participate in the regulation of oxidative stress in DN. This review clarifies the functions and mechanisms of ncRNAs in DN-related oxidative stress, providing valuable insights into the prevention, early diagnosis, and molecular therapeutic targets of DN.

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Transcriptional landscape and regulatory roles of small non-coding RNAs in the oxidative stress response of the haloarchaeon Haloferax volcanii

10.1101/218552 ◽

2017 ◽

Cited By ~ 1

Author(s):

Diego R. Gelsinger ◽

Jocelyne DiRuggiero

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Environmental Conditions ◽

Oxidative Stress Response ◽

Haloferax Volcanii ◽

Peptidase Activity ◽

Functional Roles ◽

Mrna Targets ◽

Non Coding Rnas ◽

Transcriptional Landscape

ABSTRACTHaloarchaea in their natural environment are exposed to hyper-salinity, intense solar radiation, and desiccation, all of which generate high levels of oxidative stress. Previous work has shown that Haloarchaea are an order of magnitude more resistant to oxidative stress than most mesophilic organisms. Despite this resistance, the pathways Haloarchaea use to respond to oxidative stress damage are similar to that of non-resistant organisms suggesting that regulatory processes might be key to their robustness. Recently, small non-coding RNAs (sRNAs) were discovered in Archaea under a variety of environmental conditions. We report here the transcriptional landscape and functional roles of sRNAs in the regulation of the oxidative stress response of the model haloarchaeon Haloferax volcanii. Thousands of sRNAs, both intergenic and antisense, were discovered using strand-specific sRNA-seq, comprising around 30% of the transcriptome during non-challenged and oxidative stress conditions. We identified hundreds of differentially expressed sRNAs in response to hydrogen peroxide induced oxidative stress in H. volcanii. Targets of antisense sRNAs decreased in expression when sRNAs were up-regulated indicating that sRNAs are likely playing a negative regulatory role on mRNA targets at the transcript level. Target enrichment of these antisense sRNAs included mRNAs involved in transposons mobility, chemotaxis signaling, peptidase activity, and transcription factors.IMPORTANCEWhile a substantial body of experimental work has been done to uncover functions of sRNAs in gene regulation in Bacteria and Eukarya, the functional roles of sRNAs in Archaea are still poorly understood. This study is the first to establish the regulatory effects of sRNAs on mRNAs during the oxidative stress response in the haloarchaeon Haloferax volcanii. Our work demonstrates that common principles for the response to a major cellular stress exist across the 3 domains of life while uncovering pathways that might be specific to the Archaea. This work also underscores the relevance of sRNAs in adaptation to extreme environmental conditions.

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NORHA, A Novel Follicular Atresia-related Lncrna, Promotes Granulosa Cell Apoptosis via miR-183-96-182 Cluster and FoxO1 Axis

10.21203/rs.3.rs-331387/v1 ◽

2021 ◽

Author(s):

Wang Yao ◽

Zengxiang Pan ◽

Xing Du ◽

Jinbi Zhang ◽

Honglin Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Bioinformatics Analysis ◽

Luciferase Reporter ◽

Utilization Rate ◽

Reporter Assay ◽

Follicular Atresia ◽

Rt Pcr ◽

Rna Immunoprecipitation ◽

Non Coding Rnas ◽

And Oxidative Stress

Abstract BackgroundFollicular atresia has been shown to be strongly associated with low follicle utilization rate and female infertility, which are regulated by many factors such as miroRNAs (miRNAs), a class of non-coding RNAs (ncRNAs). However, little is known about long non-coding RNAs (lncRNAs), another ncRNAs, which regulate follicular atresia. ResultsA total of 94 differentially expressed lncRNAs, including 74 up-regulated and 20 down-regulated lncRNAs, were identified in early atretic follicles compared to healthy follicles by RNA-sequencing. We identified and characterized a non-coding RNA that was highly expressed in atretic follicles (NORHA), an intergenic lncRNA, was the most significantly elevated lncRNA in early atretic follicles. Functionally, RT-PCR，flow cytometry and western blot results showed that NORHA was associated with follicular atresia by influencing GC apoptosis. Mechanistically, bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay results showed that NORHA acted as a ‘sponge’, which directly bound to the miR-183-96-182 cluster, and therefore resisted their targeting inhibition of FoxO1, the major sensor and effector of oxidative stress. Furthermore, NORHA and oxidative stress synergistically induced GC apoptosis. ConclusionsWe provide a comprehensive perspective of lncRNAs regulation of follicular atresia, and demonstrate that NORHA, a novel lncRNA related to follicular atresia, induces GC apoptosis through affecting the miR-183-96-182 cluster and Foxo1 axis

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MicroRNAs and long non-coding RNAs in the pathophysiological processes of diabetic cardiomyopathy: emerging biomarkers and potential therapeutics

Cardiovascular Diabetology ◽

10.1186/s12933-021-01245-2 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Daniel Jakubik ◽

Alex Fitas ◽

Ceren Eyileten ◽

Joanna Jarosz-Popek ◽

Anna Nowak ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Cardiomyopathy ◽

Target Genes ◽

Heart Diseases ◽

Systolic Dysfunction ◽

Left Ventricular ◽

Non Coding Rnas ◽

Potential Therapeutics

AbstractThe epidemic of diabetes mellitus (DM) necessitates the development of novel therapeutic and preventative strategies to attenuate complications of this debilitating disease. Diabetic cardiomyopathy (DCM) is a frequent disorder affecting individuals diagnosed with DM characterized by left ventricular hypertrophy, diastolic and systolic dysfunction and myocardial fibrosis in the absence of other heart diseases. Progression of DCM is associated with impaired cardiac insulin metabolic signaling, increased oxidative stress, impaired mitochondrial and cardiomyocyte calcium metabolism, and inflammation. Various non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), as well as their target genes are implicated in the complex pathophysiology of DCM. It has been demonstrated that miRNAs and lncRNAs play an important role in maintaining homeostasis through regulation of multiple genes, thus they attract substantial scientific interest as biomarkers for diagnosis, prognosis and as a potential therapeutic strategy in DM complications. This article will review the different miRNAs and lncRNA studied in the context of DM, including type 1 and type 2 diabetes and the contribution of pathophysiological mechanisms including inflammatory response, oxidative stress, apoptosis, hypertrophy and fibrosis to the development of DCM .

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