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 miR-657 Promotes Macrophage Polarization toward M1 by Targeting FAM46C in Gestational Diabetes Mellitus

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Pingping Wang ◽  
Zengfang Wang ◽  
Guojie Liu ◽  
Chengwen Jin ◽  
Quan Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Macrophage Polarization ◽  
Vital Role ◽  
Luciferase Reporter ◽  
M2 Macrophage ◽  
And Migration

MicroRNA (miRNA) has been widely suggested to play a vital role of in the pathogenesis of gestational diabetes mellitus (GDM). We have previously demonstrated that miR-657 can regulate macrophage inflammatory response in GDM. However, the role of miR-657 on M1/M2 macrophage polarization in GDM pathogenesis is not clear yet. This study is aimed at elucidating this issue and identifying novel potential GDM therapeutic targets based on miRNA network. miR-657 is found to be upregulated in placental macrophages demonstrated by real-time PCR, which can enhance macrophage proliferation and migration in vitro. Luciferase reporter assay shows the evidence that FAM46C is a target of miR-657. In addition, miR-657 can promote macrophage polarization toward the M1 phenotype by downregulating FAM46C in macrophages. The present study strongly suggests miR-657 is involved in GDM pathogenesis by regulating macrophage proliferation, migration, and polarization via targeting FAM46C. miR-657/FAM46C may serve as promising targets for GDM diagnosis and treatment.

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 Hsa_circ_0001944 promotes the growth and metastasis in bladder cancer cells by acting as a competitive endogenous RNA for miR-548

2020 ◽  
Author(s):  
Mingming Jin ◽  
Shengjie Lu ◽  
Yue Wu ◽  
Chen Yang ◽  
Chunzi Shi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Throughput Sequencing ◽  
Expression Profiles ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Invasion And Migration ◽  
And Migration

Abstract Background: Bladder cancer (BC) is a common genitourinary malignancy worldwide. Circular RNAs (circRNAs) participate in cancer development, including BC; thus, the roles of circRNAs in this process have attracted significant attention. Methods: In this study, high-throughput sequencing was used to analyze circRNA expression profiles in BC tissues. We performed RT-qPCR to determine hsa_circ_0001944 expression in BC tissues. We used fluorescence in situ hybridization (FISH) to detect hsa_circ_0001944 expression and hsa_circ_0001944 subcellular localization in BC tissues. hsa_circ_0001944 expression in BC cells was selectively regulated. We employed CCK8, transwell, and wound healing assays to monitor cell proliferation, invasion, and migration, respectively. We employed the dual-luciferase reporter and RNA pulldown assays to verify the relationships among hsa_circ_0001944, miR-548, and PROK2. We examined the effects of hsa_circ_0001944 on BC cell metastasis and proliferation in vivo using a subcutaneous xenograft model and an intravenous tail injection model in nude mice. Results: The results showed that hsa_circ_0001944 expression was significantly increased in BC samples. Furthermore, high hsa_circ_0001944 expression predicted unfavorable prognoses in BC. Functional assays validated that downregulating hsa_circ_0001944 decreased BC invasion and proliferation in vivo and in vitro. Further studies showed that hsa_circ_0001944 expression promoted BC progression via sponging miR-548 and enhancing PROK2 expression. Luciferase reporter experiments validated the interactions between hsa_circ_0001944, miR-548, and PROK2. This study also found that downregulating miR-548 or overexpressing PROK2 restored BC cell invasion and proliferation after silencing hsa_circ_0001944. Conclusions: Taken together, we found that hsa_circ_0001944 is a tumor-promoting circRNA in BC that functions as a competing endogenous RNA to regulate PROK2 expression via sponging miR-548.

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 Research Advances in the Roles of Circular RNAs in Pathophysiology and Early Diagnosis of Gestational Diabetes Mellitus

2022 ◽  
Vol 9 ◽  
Author(s):  
Yan-ping Zhang ◽  
Sha-zhou Ye ◽  
Ying-xue Li ◽  
Jia-li Chen ◽  
Yi-sheng Zhang
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Markers ◽  
Early Diagnosis ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Gestational Diabetes Mellitus ◽  
Metabolic Diseases ◽  
Circular Rna ◽  
Circular Rnas ◽  
Oral Glucose

Gestational diabetes mellitus (GDM) refers to different degrees of glucose tolerance abnormalities that occur during pregnancy or are discovered for the first time, which can have a serious impact on the mother and the offspring. The screening of GDM mainly relies on the oral glucose tolerance test (OGTT) at 24–28 weeks of gestation. The early diagnosis and intervention of GDM can greatly improve adverse pregnancy outcomes. However, molecular markers for early prediction and diagnosis of GDM are currently lacking. Therefore, looking for GDM-specific early diagnostic markers has important clinical significance for the prevention and treatment of GDM and the management of subsequent maternal health. Circular RNA (circRNA) is a new type of non-coding RNA. Recent studies have found that circRNAs were involved in the occurrence and development of malignant tumors, metabolic diseases, cardiovascular and cerebrovascular diseases, etc., and could be used as the molecular marker for early diagnosis. Our previous research showed that circRNAs are differentially expressed in serum of GDM pregnant women in the second and third trimester, placental tissues during cesarean delivery, and cord blood. However, the mechanism of circular RNA in GDM still remains unclear. This article focuses on related circRNAs involved in insulin resistance and β-cell dysfunction, speculating on the possible role of circRNAs in the pathophysiology of GDM under the current research context, and has the potential to serve as early molecular markers for the diagnosis of GDM.

scholarly journals Integrated Transcriptome Sequencing Analysis Reveals Role of miR-138-5p/ TBL1X in Placenta from Gestational Diabetes Mellitus

2018 ◽  
Vol 51 (2) ◽  
pp. 630-646 ◽  
Author(s):  
Rong Ding ◽  
Fei Guo ◽  
Yong Zhang ◽  
Xi-Mei Liu ◽  
Yu-Qian Xiang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Luciferase Assay ◽  
Control Group ◽  
Sequencing Analysis ◽  
Aberrant Expression

Background/Aims: The placenta has been suggested to play a crucial role in the pathology of gestational diabetes mellitus (GDM). Placenta-specific microRNAs (miRNAs) and the corresponding targeting genes involved in the pathology of GDM still remain to be elucidated. We aimed to identify the dysregulated miRNAs and the corresponding mRNA targets through an integrated miRNA and mRNA transcriptomic profiles analysis and investigate the role of differentially expressed miR-138-5p/TBL1X in GDM. Methods: RNA sequencing (RNA-seq) was performed in 16 placentas from GDM and control group. Differentially expressed mRNAs and miRNAs in GDM were validated by quantitative PCR (qPCR). The wound healing assay and transwell migration assay were used to analyze cell migration ability. The cell proliferation was determined by CCK8 assay. Luciferase assay was used to confirm the direct binding of the targeted TBL1X with miR-138-5p. Results: Totally, 281 mRNAs and 32 miRNAs were found to be differentially expressed in the GDM placentas. The biological relationships of the miRNA/mRNA pairs were related to cellular development and function and organ morphology. Among the aberrantly expressed molecules, we selected miR-138-5p from the bioinformatics analysis and found that miR-138-5p significantly inhibited the migration and proliferation of trophoblasts (HTR-8/SVneo) by targeting the 3’-UTR of TBL1X. Furthermore, the aberrant expression of miR-138-5p and TBL1X was significantly correlated with the weight of the placenta. Conclusion: We present the first integrative analysis of miRNA and mRNA expression profiles in GDM placenta and uncover a more detailed role for miR-138-5p, as well as its target TBL1X in the pathology of GDM.

scholarly journals Hsa_circ_0001944 promotes the growth and metastasis in bladder cancer cells by acting as a competitive endogenous RNA for miR-548

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Mingming Jin ◽  
Shengjie Lu ◽  
Yue Wu ◽  
Chen Yang ◽  
Chunzi Shi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Throughput Sequencing ◽  
Expression Profiles ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Invasion And Migration ◽  
And Migration

Abstract Background Bladder cancer (BC) is a common genitourinary malignancy worldwide. Circular RNAs (circRNAs) participate in cancer development, including BC; thus, the roles of circRNAs in this process have attracted significant attention. Methods In this study, high-throughput sequencing was used to analyze circRNA expression profiles in BC tissues. We performed RT-qPCR to determine hsa_circ_0001944 expression in BC tissues. We used fluorescence in situ hybridization (FISH) to detect hsa_circ_0001944 expression and hsa_circ_0001944 subcellular localization in BC tissues. hsa_circ_0001944 expression in BC cells was selectively regulated. We employed CCK8, transwell, and wound healing assays to monitor cell proliferation, invasion, and migration, respectively. We employed the dual-luciferase reporter and RNA pulldown assays to verify the relationships among hsa_circ_0001944, miR-548, and PROK2. We examined the effects of hsa_circ_0001944 on BC cell metastasis and proliferation in vivo using a subcutaneous xenograft model and an intravenous tail injection model in nude mice. Results The results showed that hsa_circ_0001944 expression was significantly increased in BC samples. Furthermore, high hsa_circ_0001944 expression predicted unfavorable prognoses in BC. Functional assays validated that downregulating hsa_circ_0001944 decreased BC invasion and proliferation in vivo and in vitro. Further studies showed that hsa_circ_0001944 expression promoted BC progression via sponging miR-548 and enhancing PROK2 expression. Luciferase reporter experiments validated the interactions between hsa_circ_0001944, miR-548, and PROK2. This study also found that downregulating miR-548 or overexpressing PROK2 restored BC cell invasion and proliferation after silencing hsa_circ_0001944. Conclusions Taken together, we found that hsa_circ_0001944 is a tumor-promoting circRNA in BC that functions as a competing endogenous RNA to regulate PROK2 expression via sponging miR-548.

scholarly journals Non-Coding RNAs and Extracellular Vehicles: Their Role in the Pathogenesis of Gestational Diabetes Mellitus

2021 ◽  
Vol 12 ◽  
Author(s):  
Tie-Ning Zhang ◽  
Wei Wang ◽  
Xin-Mei Huang ◽  
Shan-Yan Gao
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Early Identification ◽  
Specific Treatment ◽  
Circular Rnas ◽  
Third Trimester ◽  
Considerable Impact ◽  
Non Coding Rnas

Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first recognition in the second or third trimester of pregnancy. GDM has a considerable impact on health outcomes of the mother and offspring during pregnancy, delivery, and beyond. Although the exact mechanism regarding GDM remains unclear, numerous studies have suggested that non-coding RNAs, including long non-coding (lnc)RNAs, microRNAs, and circular RNAs, were involved in the pathogenesis of GDM in which they played vital regulatory roles. Additionally, several studies have revealed that extracellular vehicles also participated in the pathogenesis of GDM, highlighting their important role in this disease. Considering the lack of effective biomarkers for the early identification of and specific treatment for GDM, non-coding RNAs and extracellular vehicles may be promising biomarkers and even targets for GDM therapies. This review provides an update on our understanding of the role of non-coding RNAs and extracellular vehicles in GDM. As our understanding of the function of lncRNAs and extracellular vehicles improves, the future appears promising for their use as potential biomarkers and treatment targets for GDM in clinical practice.

scholarly journals Suppression of PNPase Alleviates Gestational Diabetes Mellitus-cardiovascular Injury through Up-regulating MicroRNA-26a and Down-regulating PTEN

2021 ◽  
Author(s):  
Li Liu ◽  
Haiying Wu# ◽  
Xianghong Cheng
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Saturated Fat ◽  
Scratch Test ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
And Migration

Abstract Objective: Gestational diabetes mellitus (GDM) is often accompanied by cardiovascular injury (CI), while the specific pathology remains largely unknown. The purpose of this study was to investigate the role of Polynucleotide Phosphorylase (PNPase) in GDM-CI.Methods: GDM-CI rats were modeled by giving high-glucose and high-saturated fat compound feed, and PNPase and miR-26a expression in rats was determined. Vascular smooth muscle cells (VSMCs) were isolated, and cells were transfected with si-PNPase, miR-26a mimic, or si-PNPase + miR-26a inhibitor. Cell proliferation, apoptosis and migration of VSMCs were measured by CCK-8 assay, flow cytometry, and scratch test. Dual-luciferase reporter gene assay was performed to verify the targeting relationship between miR-26a and PTEN. RT-qPCR was implemented to detect the expression levels of miR-26a and PTEN among cells in each group.Results: GDM-CI increased PNPase expression and decreased miR-26a expression in cardiovascular tissues of GDM-CI rats. Silencing PNPase and miR-26a upregulation reduced VSMC apoptosis, and enhanced proliferation and migration abilities in GDM-CI. Treatment with miR-26a inhibitor reversed the alleviating effect of inhibiting PNPase expression on GDM-CI. There was a targeting relationship between miR-26a and PTEN, and miR-26a mimic inhibited the expression of PTEN. Suppressed PTEN was found to relieve the GDM-CI.Conclusion: This study suggests that suppression of PNPase alleviates GDM-CI through up-regulating miR-26a and down-regulating PTEN.

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