Altered levels of MALAT1 and H19 derived from serum or serum exosomes associated with type-2 diabetes

Tello‐Flores, Vianet Argelia; Valladares‐Salgado, Adán; Ramírez‐Vargas, Marco Antonio; Cruz, Miguel; del-Moral-Hernández, Oscar; Cahua-Pablo, José Ángel; Ramı́rez, Mónica; Hernández-Sotelo, Daniel; Armenta-Solís, Adakatia; Flores‐Alfaro, Eugenia

doi:10.1016/j.ncrna.2020.03.001

Cited by 38 publications

(24 citation statements)

References 34 publications

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“…These biovesicles are present in various body fluids including plasma, serum, lymph, urine, and cerebrospinal fluid [ 16 ]. Thus study of these biovesicles is possibly a suitable way to find biomarker for early detection, diagnosis, prevention, prognosis, and targeted therapy of various diseases like DN [ 9 , 17 – 19 ]. In this instance, WT1 mRNA gene expression in urinary exosome of DN patients showed significant correlation with the reduction of estimated glomerular filtration rate (eGFR) representing renal function.…”

Section: Introductionmentioning

confidence: 99%

WT1 and ACE mRNAs of blood extracellular vesicle as biomarkers of diabetic nephropathy

et al. 2021

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Background Diabetic nephropathy (DN) has an increasing global prevalence with excessive health expenditure and burden. Exosomal mRNAs regulate intercellular communications and participate in the pathogenesis of various disorders like DN. This study aimed to assess the expression levels of ACE, ELMO1, and WT1 mRNAs in the blood extracellular vesicles (EVs) of DN patients and diabetic patients without nephropathy (DM group) in comparison to healthy controls and investigate their correlations with the severity of DN. Methods The performed investigation is a cross-sectional study of 256 participants including 103 DN patients, 100 DM patients, and 53 healthy controls. The quantification of WT1, ACE, and ELMO1 mRNAs in the blood EVs were executed using qRT-PCR. The ROC analysis was performed to determine the diagnostic accuracy of mRNAs. Results DN patients had significantly higher expressed WT1 mRNA (1.70-fold change) and lower expressed ACE mRNA (0.55-fold change) in the blood EVs compared to DM patients and controls. ELMO1 mRNA was not expressed in EVs of any groups. A positive correlation between WT1 mRNA level and urine Alb/Cr ratio (r = 0.602, p < 0.001) and a negative correlation between ACE mRNA expression and urine Alb/Cr ratio within DN patients (r = − 0.474, p < 0.001) was identified. The accuracy of WT1 mRNA and 1/ACE mRNA for predicting incipient DN was 0.63 (95% CI 0.55, 0.72) and 0.62 (95% CI 0.54, 0.71), and for predicting overt DN was 0.83 (95% CI 0.74, 0.92) and 0.75 (95% CI 0.66, 0.83), respectively. Conclusions WT1 and ACE mRNAs level in blood EVs were predictors for early diagnosis of DN therefore their quantifications might be used to determine the severity of albuminuria and glomerular injuries.

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Section: Introductionmentioning

confidence: 99%

WT1 and ACE mRNAs of blood extracellular vesicle as biomarkers of diabetic nephropathy

et al. 2021

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“…Consequently, as Fawzy et al [44] demonstrated in their study, H19 levels are significantly higher in plasma of T2D patients, though a receiver operating characteristics (ROC) analysis was not performed. Additionally, Tello-Flores et al [106] demonstrated in their study that the relative expression of serum H19 was two-fold higher among patients with impaired glycemic control when compared to diabetics with proper glucose control. Furthermore, an association between T2D susceptibility and genetic variants of both H19 and MEG3 was demonstrated [107].…”

Section: Prognostic Potentialmentioning

confidence: 95%

Non-Coding RNAs as Potential Novel Biomarkers for Early Diagnosis of Hepatic Insulin Resistance

Pielok

Marycz

2020

IJMS

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In the recent years, the prevalence of metabolic conditions such as type 2 Diabetes (T2D) and metabolic syndrome (MetS) raises. The impairment of liver metabolism resulting in hepatic insulin resistance is a common symptom and a critical step in the development of T2D and MetS. The liver plays a crucial role in maintaining glucose homeostasis. Hepatic insulin resistance can often be identified before other symptoms arrive; therefore, establishing methods for its early diagnosis would allow for the implementation of proper treatment in patients before the disease develops. Non-coding RNAs such as miRNAs (micro-RNA) and lncRNAs (long-non-coding RNA) are being recognized as promising novel biomarkers and therapeutic targets—especially due to their regulatory function. The dysregulation of miRNA and lncRNA activity has been reported in the livers of insulin-resistant patients. Many of those transcripts are involved in the regulation of the hepatic insulin signaling cascade. Furthermore, for several miRNAs (miR-802, miR-499-5p, and miR-122) and lncRNAs (H19 imprinted maternally expressed transcript (H19), maternally expressed gene 3 (MEG3), and metastasis associated lung adenocarcinoma transcript 1 (MALAT1)), circulating levels were altered in patients with prediabetes, T2D, and MetS. In the course of this review, the role of the aforementioned ncRNAs in hepatic insulin signaling cascade, as well as their potential application in diagnostics, is discussed. Overall, circulating ncRNAs are precise indicators of hepatic insulin resistance in the development of metabolic diseases and could be applied as early diagnostic and/or therapeutic tools in conditions associated with insulin resistance.

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“…At least two studies have reported the elevated expression of H19 in blood plasma samples from diabetic patients compared to healthy patients [ 65 , 67 ]. In contrast, our group identified low H19 expression in blood serum samples from patients with metabolic syndrome [ 68 ]. The contradictory results for the expression of H19, as well as the variability in the clinical characteristics of the patients, such as the timing in the progression of IR or T2D, the metabolic control, and the treatment, could contribute to the variation in the expression of lncRNAs.…”

Section: Lncrnas In Insulin Resistancementioning

confidence: 99%

Role of Long Non-Coding RNAs and the Molecular Mechanisms Involved in Insulin Resistance

Tello‐Flores

Beltrán-Anaya

Ramírez‐Vargas

et al. 2021

IJMS

Self Cite

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Long non-coding RNAs (lncRNAs) are single-stranded RNA biomolecules with a length of >200 nt, and they are currently considered to be master regulators of many pathological processes. Recent publications have shown that lncRNAs play important roles in the pathogenesis and progression of insulin resistance (IR) and glucose homeostasis by regulating inflammatory and lipogenic processes. lncRNAs regulate gene expression by binding to other non-coding RNAs, mRNAs, proteins, and DNA. In recent years, several mechanisms have been reported to explain the key roles of lncRNAs in the development of IR, including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), imprinted maternal-ly expressed transcript (H19), maternally expressed gene 3 (MEG3), myocardial infarction-associated transcript (MIAT), and steroid receptor RNA activator (SRA), HOX transcript antisense RNA (HOTAIR), and downregulated Expression-Related Hexose/Glucose Transport Enhancer (DREH). LncRNAs participate in the regulation of lipid and carbohydrate metabolism, the inflammatory process, and oxidative stress through different pathways, such as cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), polypyrimidine tract-binding protein 1/element-binding transcription factor 1c (PTBP1/SREBP-1c), AKT/nitric oxide synthase (eNOS), AKT/forkhead box O1 (FoxO1), and tumor necrosis factor-alpha (TNF-α)/c-Jun-N-terminal kinases (JNK). On the other hand, the mechanisms linked to the molecular, cellular, and biochemical actions of lncRNAs vary according to the tissue, biological species, and the severity of IR. Therefore, it is essential to elucidate the role of lncRNAs in the insulin signaling pathway and glucose and lipid metabolism. This review analyzes the function and molecular mechanisms of lncRNAs involved in the development of IR.

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Altered levels of MALAT1 and H19 derived from serum or serum exosomes associated with type-2 diabetes

Cited by 38 publications

References 34 publications

WT1 and ACE mRNAs of blood extracellular vesicle as biomarkers of diabetic nephropathy

WT1 and ACE mRNAs of blood extracellular vesicle as biomarkers of diabetic nephropathy

Non-Coding RNAs as Potential Novel Biomarkers for Early Diagnosis of Hepatic Insulin Resistance

Role of Long Non-Coding RNAs and the Molecular Mechanisms Involved in Insulin Resistance

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