Circular RNA expression profiles in placental villi from women with gestational diabetes mellitus

2018 ◽  
Vol 498 (4) ◽  
pp. 743-750 ◽  
Author(s):  
Linping Yan ◽  
Jie Feng ◽  
Feng Cheng ◽  
Xianwei Cui ◽  
Lingjuan Gao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Expression Profiles ◽  
Circular Rna ◽  
Rna Expression ◽  
Placental Villi

scholarly journals Circular RNA expression profiles in umbilical cord blood exosomes from normal and gestational diabetes mellitus patients

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Minkai Cao ◽  
Le Zhang ◽  
Yu Lin ◽  
Zhengying Li ◽  
Jianjuan Xu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Expression Profiles ◽  
Circular Rna ◽  
Cellular Functions ◽  
Pathway Analyses

Abstract Circular RNA (circRNA) is a novel member of endogenous noncoding RNAs with widespread distribution and diverse cellular functions. Recently, circRNAs have been identified for their enrichment and stability in exosomes. However, the roles of circRNAs from umbilical cord blood exosomes in gestational diabetes mellitus (GDM) occurrence and fetus growth remains poorly understood. In the present study, we used microarray technology to construct a comparative circRNA profiling of umbilical cord blood exosomes between GDM patients and controls. We found the exosome particle size was larger, and the exosome concentration was higher in the GDM patients. A total of 88,371 circRNAs in umbilical cord blood exosomes from two groups were evaluated. Of these, 229 circRNAs were significantly up-regulated and 278 circRNAs were significantly down-regulated in the GDM patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses demonstrated that circRNA parental genes involved in the regulation of metabolic process, growth and development were significantly enriched, which are important in GDM development and fetus growth. Further circRNA/miRNA interactions analysis showed that most of the exosomal circRNAs harbored miRNA binding sites, and some miRNAs were associated with GDM. Collectively, these results lay a foundation for extensive studies on the role of exosomal circRNAs in GDM development and fetus growth.

scholarly journals Circulating exosomal hsa_circRNA_0039480 is highly expressed in gestational diabetes mellitus and may be served as a biomarker for early diagnosis of GDM

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Bao Jiang ◽  
Junfeng Zhang ◽  
Xiubin Sun ◽  
Chunyan Yang ◽  
Guanghui Cheng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Expression Profiles ◽  
Pearson Correlation ◽  
First Trimester ◽  
Circular Rna ◽  
Diagnostic Value ◽  
Pathological Process ◽  
Pcr Analysis

Abstract Background Gestational diabetes mellitus (GDM) seriously affects the health of mothers and babies, and there are still no effective early diagnostic markers. Therefore, it is necessary to find diagnostic biomarkers for screening GDM in early pregnancy. Circular RNA (circRNA) is more stable than linear RNA, and can be encapsulated in exosomes and participate in the pathological process of various diseases, which makes it a better candidate biomarker for various diseases. In this study, we attempted to identify the exosomal circRNA biomarkers for detecting early GDM. Methods We performed microarray analysis to compare the plasma exosomal circRNA expression profiles of three GDM patients 48 h before and 48 h after delivery. The repeatability of the expression of circRNAs were randomly validated by RT-PCR analysis. Pearson correlation analysis was applied to evaluate the correlation between circRNAs and OGTT level. ROC curve was established to assess the diagnostic value of circRNAs for GDM at different stages. Results Plasma exosomal hsa_circRNA_0039480 and hsa_circRNA_0026497 were highly expressed in GDM patients before delivery (P < 0.05). The hsa_circRNA_0039480 expression was higher for GDM group than NGT group at different stages, and was also positively correlated with OGTT during the second trimester (P < 0.05). The expression of hsa_circRNA_0026497 was higher for GDM group during the third, and second trimesters. And there was a strong correlation between two circRNAs in GDM patients during the first-trimester (r = 0.496, P = 0.014). Hsa_circRNA_0039480 showed significant diagnostic value in the first, second, and third trimesters of pregnancy (AUC = 0.704, P = 0.005; AUC = 0.898, P < 0.001 and AUC = 0.698, P = 0.001, respectively). Notably, the combination of hsa_circRNA_0039480 and hsa_circRNA_0026497 exhibited promising discriminative effect on GDM in the first trimesters (AUC = 0.754, P < 0.001). Conclusion Plasma exosomal hsa_cirRNA_0039480 is highly expressed in GDM patients at different stages and may be served as a candidate biomarker for early detection of GDM.

scholarly journals Circulating Exosomal hsa_circRNA_0039480 is Highly Expressed in Gestational Diabetes Mellitus and May Be Served As A Biomarker for Early Diagnosis of GDM

2021 ◽  
Author(s):  
Bao Jiang ◽  
Junfeng Zhang ◽  
Xiubin Sun ◽  
Chunyan Yang ◽  
Guanghui Cheng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Expression Profiles ◽  
Pearson Correlation ◽  
First Trimester ◽  
Circular Rna ◽  
Diagnostic Value ◽  
Pathological Process ◽  
Pcr Analysis

Abstract Background: Gestational diabetes mellitus (GDM) seriously affects the health of mothers and babies, and there are still no effective early diagnostic markers. Therefore, it is necessary to find diagnostic biomarkers for screening GDM in early pregnancy. Circular RNA (circRNA) is more stable than linear RNA, and can be encapsulated in exosomes and participate in the pathological process of various diseases, which makes it a better candidate biomarker for various diseases. In this study, we attempted to identify the exosomal circRNA biomarkers for detecting early GDM.Methods: We performed microarray analysis to compare the plasma exosomal circRNA expression profiles of three GDM patients 48 hours before and 48 hours after delivery. The repeatability of the expression of circRNAs were randomly validated by RT-PCR analysis. Pearson correlation analysis was applied to evaluate the correlation between circRNAs and circRNA-OGTT level. ROC curve was established to assess the diagnostic value of circRNAs for GDM at different stages.Results: Plasma exosomal hsa_circRNA_0039480 and hsa_circRNA_0026497 were highly expressed in GDM patients before delivery(P<0.05). The hsa_circRNA_0039480 expression was higher for GDM group than NGT group at different stages, and was also positively correlated with OGTT during the second trimester (P<0.05). The expression of hsa_circRNA_0026497 was higher for GDM group during the third, and second trimesters. And there was a strong correlation between two circRNAs in GDM patients during the first-trimester (r =0.496, P=0.014). Hsa_circRNA_0039480 showed significant diagnostic value in the first, second, and third trimesters of pregnancy (AUC = 0.704, P=0.005; AUC = 0.898, P < 0.001 and AUC = 0.698, P= 0.001, respectively). Notably, the combination of hsa_circRNA_0039480 and hsa_circRNA_0026497 exhibited promising discriminative effect on GDM in the first trimesters (AUC=0.754, P < 0.001).Conclusion: Plasma exosomal hsa_cirRNA_0039480 is highly expressed in GDM patients and may be served as a candidate biomarker for early detection of GDM.

scholarly journals The role of circular RNA circ_0008285 in gestational diabetes mellitus by regulating the biological functions of trophoblasts

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Haitian Chen ◽  
Shaofeng Zhang ◽  
Yanxin Wu ◽  
Zhuyu Li ◽  
Dongyu Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
High Throughput Sequencing ◽  
Expression Profiles ◽  
Circular Rna ◽  
Circular Rnas ◽  
Invasion And Migration ◽  
And Migration

Abstract Background Circular RNAs (circRNAs) has emerged as vital regulator involved in various diseases. In this study, we identified and investigated the potential circRNAs involved in gestational diabetes mellitus (GDM). Methods High-throughput sequencing was used to collect the plasma circRNAs expression profiles of GDM patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to measure the expressions of circ_0008285 and circ_0001173 in the plasma specimens. The Pearson’s correlation test was employed to assess the correlation between 2 circRNAs expression and the clinicopathologic data. Two circRNAs expression was verified in high glucose (HG)-induced HTR-8/SVneo cells. MTS, transwell assay was used to evaluate the effects of circ_0008285 expression on HG-induced HTR-8/SVneo cells. The network of circ_0008285 was constructed using cytocape. Results In GDM patients, the expression of circ_0008285 was significantly upregulated, while that of circ_0001173 was decreased. Circ_0008285 was significantly correlated with the total cholesterol and LDL-C levels. Circ_0001173 was significantly correlated with glycated hemoglobin. HG promoted the proliferation, invasion, and migration in HTR-8/SVneo cells, while the knockdown of circ_0008285 exerted reverse effects. In addition, network construction exhibited that circ_0008285 had 45 miRNA binding sites, which correlated with 444 mRNA. Conclusions circ_0008285 plays an important role and provides a clue for the usage of therapeutic targets in the development of GDM.

scholarly journals Identification of a novel association for the WWOX/HIF1A axis with gestational diabetes mellitus (GDM)

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10604
Author(s):  
Izabela Baryla ◽  
Elzbieta Pluciennik ◽  
Katarzyna Kośla ◽  
Marzena Wojcik ◽  
Andrzej Zieleniak ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glucose Metabolism ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Expression Profiles ◽  
Hypoxia Inducible Factor ◽  
Gene Expression Profiles ◽  
Normal Pregnancy ◽  
Normal Tissues ◽  
Genes Encoding

Background Although the WW-domain-containing oxidoreductase (WWOX)/Hypoxia-inducible factor 1 (HIF1) pathway is a well-known regulator of cellular glucose and energy metabolism in pathophysiological processes, its role in gestational diabetes mellitus (GDM), remains elusive. We undertook this study to determine the effect of WWOX/HIF1A signaling on the expression of glucose metabolism genes in GDM patients. Methods Leukocytes were obtained from 135 pregnant women with (n = 98) or without (n = 37) GDM and, in turn, 3 months (n = 8) and 1 year (n = 12) postpartum. Quantitative RT-PCR was performed to determine gene expression profiles of the WWOX/HIF1A-related genes, including those involved in glucose transport (SLC2A1, SLC2A4), glycolytic pathway (HK2, PKM2, PFK, LDHA), Wnt pathway (DVL2, CTNNB1), and inflammatory response (NFKB1). Results GDM patients displayed a significant downregulation of WWOX with simultaneous upregulation of HIF1A which resulted in approximately six times reduction in WWOX/HIF1A ratio. As a consequence, HIF1A induced genes (SLC2A1, HK2, PFK, PKM) were found to be overexpressed in GDM compared to normal pregnancy and negative correlate with WWOX/HIF1A ratio. The postpartum WWOX expression was higher than during GDM, but its level was comparable to that observed in normal pregnancy. Conclusions The obtained results suggest a significant contribution of the WWOX gene to glucose metabolism in patients with gestational diabetes. Decreased WWOX expression in GDM compared to normal pregnancy, and in particular reduction of WWOX/HIF1A ratio, indicate that WWOX modulates HIF1α activity in normal tissues as described in the tumor. The effect of HIF1α excessive activation is to increase the expression of genes encoding proteins directly involved in the glycolysis which may lead to pathological changes in glucose metabolism observed in gestational diabetes.

scholarly journals STRA6 and Placental Retinoid Metabolism in Gestational Diabetes Mellitus

2021 ◽  
Vol 11 (12) ◽  
pp. 1301
Author(s):  
Arrigo Fruscalzo ◽  
Luigi Viola ◽  
Maria Orsaria ◽  
Stefania Marzinotto ◽  
Michela Bulfoni ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Expression Pattern ◽  
Staining Pattern ◽  
Control Group ◽  
Rna Expression ◽  
Retrospective Case ◽  
Altered Expression ◽  
Retinoid Metabolism

Background: Recent reports indicate the potential role of the stimulated by retinoic acid 6 (STRA6) protein in developing insulin resistance. The study’s objective was to assess placental STRA6 expression and staining pattern in human pregnancy complicated by gestational diabetes mellitus (GDM). The expression pattern of further relevant genes involved in retinoid metabolism was also evaluated. Methods: A retrospective case–control study on paraffin-embedded placental tissue. Twenty-two human pregnancies affected by GDM, namely, 11 insulin-treated (iGDM) and 11 diet-controlled (dGDM), were compared with 22 normal-developed pregnancies (controls). An RT-PCR was performed in a random sample of 18 patients (six iGDM, six dGDM, and six controls) to assess RNA expression of STRA6 and further markers of retinoid metabolism. A semi-quantitative intensity evaluation at immunohistochemistry was performed for STRA6 in all 44 recruited patients. Results: STRA6 showed a decreased placental staining (9.09% vs. 68.18% positively stained samples, p < 0.05) and augmented RNA expression in dGDM patients than controls (ΔCT expression 0.473, IQR 0.403–0.566 vs. 0.149, IQR 0.092–0.276, p < 0.05). The protein staining pattern in patients affected by iGDM was comparable to controls. A reduced RNA expression of LPL, LRP1, VLDLR, and MTTP besides an augmented expression of LDLR was found in dGDM, while overexpression of LRP1 and LPL was found in iGDM patients. Unlike in the control group, significant positive correlations were found between RXRα and the proteins involved in the intracellular uptake of ROH, such as STRA6, LRP1, LRP2, and VLDLR. Conclusions: An altered placental expression and staining pattern of STRA6 were found in pregnancies complicated by GDM compared to the controls. These changes were coupled to an altered expression pattern of several other genes involved in the retinoid metabolism.

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