The Big Entity of New RNA World: Long Non-Coding RNAs in Microvascular Complications of Diabetes

Raut, Satish K; Khullar, Madhu

doi:10.3389/fendo.2018.00300

Cited by 38 publications

(24 citation statements)

References 85 publications

(88 reference statements)

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“…Finally, long non-coding RNA (lncRNAs) is a novel class of RNA that does not code for proteins and are important regulators of gene expression. Recent studies have found that diabetes correlates with an aberrant expression of these molecules ( Raut and Khullar, 2018 ). Briefly, lncRNA-myocardial infarction-associated transcript (MIAT) expression is upregulated in models of diabetic cardiomyopathy and when knocked down, there are improvements in cardiac function and a decrease in cardiomyocyte apoptosis ( Zhang et al, 2016 ; Zhou et al, 2017 ).…”

Section: New Potential Targets For Future Therapiesmentioning

confidence: 99%

Diabetic Cardiomyopathy: Current and Future Therapies. Beyond Glycemic Control

et al. 2018

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Diabetes mellitus and the associated complications represent a global burden on human health and economics. Cardiovascular diseases are the leading cause of death in diabetic patients, who have a 2–5 times higher risk of developing heart failure than age-matched non-diabetic patients, independent of other comorbidities. Diabetic cardiomyopathy is defined as the presence of abnormal cardiac structure and performance in the absence of other cardiac risk factors, such coronary artery disease, hypertension, and significant valvular disease. Hyperglycemia, hyperinsulinemia, and insulin resistance mediate the pathological remodeling of the heart, characterized by left ventricle concentric hypertrophy and perivascular and interstitial fibrosis leading to diastolic dysfunction. A change in the metabolic status, impaired calcium homeostasis and energy production, increased inflammation and oxidative stress, as well as an accumulation of advanced glycation end products are among the mechanisms implicated in the pathogenesis of diabetic cardiomyopathy. Despite a growing interest in the pathophysiology of diabetic cardiomyopathy, there are no specific guidelines for diagnosing patients or structuring a treatment strategy in clinical practice. Anti-hyperglycemic drugs are crucial in the management of diabetes by effectively reducing microvascular complications, preventing renal failure, retinopathy, and nerve damage. Interestingly, several drugs currently in use can improve cardiac health beyond their ability to control glycemia. GLP-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors have been shown to have a beneficial effect on the cardiovascular system through a direct effect on myocardium, beyond their ability to lower blood glucose levels. In recent years, great improvements have been made toward the possibility of modulating the expression of specific cardiac genes or non-coding RNAs in vivo for therapeutic purpose, opening up the possibility to regulate the expression of key players in the development/progression of diabetic cardiomyopathy. This review summarizes the pathogenesis of diabetic cardiomyopathy, with particular focus on structural and molecular abnormalities occurring during its progression, as well as both current and potential future therapies.

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Section: New Potential Targets For Future Therapiesmentioning

confidence: 99%

Diabetic Cardiomyopathy: Current and Future Therapies. Beyond Glycemic Control

et al. 2018

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“…Long noncoding RNAs (lncRNA), a newly discovered type of RNA transcripts with more than 200 nucleotides, were proved to regulate gene expression and progression of complex human diseases . As lncRNA lacks protein‐coding potential, it was previously defined to be transcriptional “noise.” However, more and more data show that lncRNA possess critical functions in various tissues and cell types …”

Section: Introductionmentioning

confidence: 99%

The lncRNA SNHG15/miR‐18a‐5p axis promotes cell proliferation in ovarian cancer through activating Akt/mTOR signaling pathway

Zhang

Jiang

Qiao

2020

J of Cellular Biochemistry

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Here, we report the expression pattern, function and regulatory mechanism of SNHG15 together with miR-18a-5p micro RNA in ovarian cancer (OC) for the first time. We recruited 20 patients and took normal ovarian tissues and ovarian tumor tissues from them. We used cell culture, transfection, in vivo tumor xenograft assay, and multiple types of detection assays to investigate the expression and regulation of long noncoding RNA (lncRNA) SNHG15/miR-18a-5p in ovarian tissues and cells. Results: We found that the messenger RNA expression level of SNHG15 was significantly higher and miR-18 was decreased in ovarian cancer tissues and in OC cells. Functional experiments showed that SNHG15 overexpression potentiated the migration and invasion of OC cells, while SNHG15 inhibition reduced the tumor proliferation, which was restored via overexpression of miR-18a. SNHG15 was found to directly target and suppress the expression of miR-18a. Our results illustrate the possible molecular mechanism of lncRNA SNHG15/miR-18a-5p functions in cell proliferation in OC. SNHG15/miR-18a promoted the progression of OC cells via the protein kinase B/mammalian target of rapamycin signaling pathway.

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“…Among other lncRNAs which act as regulators of diabetic tubular injury in DKD 39 , 40 , 41 , the expression of lncRNA MIAT was reduced and negatively correlated with serum creatinine and blood urea nitrogen levels 24 , 42 . It is assumed that lncRNAs could be potential regulators of high glucose-induced renal tubular injury.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNAs may impact podocytes and proximal tubule function through modulating miRNAs expression in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus patients

Petrică¹,

Hogea²,

Gădălean³

et al. 2021

Int. J. Med. Sci.

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Aims: Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aims of the study were to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients in relation to a particular miRNAs profile. Methods: A total of 136 patients with type 2 DM and 25 healthy subjects were assessed in a cross-sectional study concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and of proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), urinary miRNA21, 124, 93, 29a. Results: Multivariable regression analysis showed that urinary lncMALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93, 29a (p<0.0001; R 2 =0.727); urinary lncNEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, 29a (p<0.0001; R 2 =0.702); urinary lncMIAT correlated directly with miRNA93 and 29a, eGFR (p<0.0001; R 2 =0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, 124 (p<0.0001; R 2 =0.654); urinary lncTUG1 correlated directly with eGFR, miRNA93, 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, 124 (p<0.0001; R 2 =0.748). Conclusions: In patients with type 2 DM lncRNAs exert either deleterious or protective functions within glomeruli and PT. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.

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The Big Entity of New RNA World: Long Non-Coding RNAs in Microvascular Complications of Diabetes

Cited by 38 publications

References 85 publications

Diabetic Cardiomyopathy: Current and Future Therapies. Beyond Glycemic Control

Diabetic Cardiomyopathy: Current and Future Therapies. Beyond Glycemic Control

The lncRNA SNHG15/miR‐18a‐5p axis promotes cell proliferation in ovarian cancer through activating Akt/mTOR signaling pathway

Long noncoding RNAs may impact podocytes and proximal tubule function through modulating miRNAs expression in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus patients

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