Diagnostic value of candidate noncoding RNAs in leukocytes of patients with gestational diabetes mellitus

Hu, Jialei; Mu, Hanyou; Gao, Linshan; Pan, Ying; Wu, Chuanfei; Zhang, Dong; Chen, Qiaojun; Ding, Honghui

doi:10.3892/etm.2020.9576

Cited by 7 publications

(4 citation statements)

References 32 publications

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“…PAX8-AS1 is a non-coding RNA that is involved in the pathology of the disease despite its inability to encode protein synthesis. In a study examining non-coding RNA in leukocytes from patients with gestational diabetes mellitus (GDM), PAX8-AS1 expression levels were significantly lower in GDM patients compared to healthy pregnant women and could be used as a diagnostic biomarker for GDM ( 46 ). The rest of key genes need to be further studied in the future.…”

Section: Discussionmentioning

confidence: 99%

The transcriptomic and epigenetic alterations in type 2 diabetes mellitus patients of Chinese Tibetan and Han populations

et al. 2023

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BackgroundDue to the distinctive living environment, lifestyle, and diet, the Tibetan community in China has the lowest prevalence of T2DM and prediabetes among numerous ethnic groups, while Han community shows the highest statistic. In this study, we aim to conclude the clinical manifestations of both Tibetan and Han T2DM patients and their association with transcriptomic and epigenetic alterations.MethodsA cross-sectional study including 120 T2DM patients from Han and Tibetan ethnic groups were conducted between 2019 to 2021 at the Hospital of Chengdu University of Traditional Chinese Medicine. The various clinical features and laboratory tests were recorded and analyzed between the two groups. The genome-wide methylation pattern and RNA expression were determined by Reduced Representation Bisulfite Sequencing (RBBS) and Poly (A) RNA sequencing (RNA-seq) from leucocytes of peripheral blood samples in 6 Han and 6 Tibetan patients. GO analysis and KEGG analysis were conducted in differentially expressed genes and those with differentially methylated regions.ResultsCompared to Han, Tibetan T2DM individuals intake more coarse grains, meat and yak butter, but less refined grains, vegetables and fruit. They also showed increased BMI, Hb, HbA1c, LDL, ALT, GGT and eGFR, and decreased level of BUN. Among the 12 patients in the exploratory cohort, we identified 5178 hypomethylated and 4787 hypermethylated regions involving 1613 genes in the Tibetan group. RNA-seq showed a total of 947 differentially expressed genes (DEGs) between the two groups, with 523 up-regulated and 424 down-regulated in Tibetan patients. By integrating DNA methylation and RNA expression data, we identified 112 DEGs with differentially methylated regions (overlapping genes) and 14 DEGs with promoter-related DMRs. The functional enrichment analysis demonstrated that the overlapping genes were primarily involved in metabolic pathways, PI3K-Akt signaling pathway, MAPK signaling pathway, pathways in cancer and Rap1 signaling pathway.ConclusionOur study demonstrates the clinical characteristics of T2DM differ subtly between various ethnic groups that may be related to epigenetic modifications, thus providing evidence and ideas for additional research on the genetic pattern of T2DM.

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Section: Discussionmentioning

confidence: 99%

The transcriptomic and epigenetic alterations in type 2 diabetes mellitus patients of Chinese Tibetan and Han populations

et al. 2023

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“…Stirm et al (60) reported conflicting results on the expression of let-7g. These authors reported higher expression of let-7g in the screening group, however, no difference was observed in the validation group in whole blood samples of German women with GDM compared to controls in the screening group (60) Other articles included in this review reported differential miRNA expression, yet these miRNAs were identified in single studies only (36,37,43,44,48,50,57,59,69,71,74,76,77,80,81).…”

Section: Qualitative Synthesis Of Studiesmentioning

confidence: 87%

“…Other articles included in this review reported differential miRNA expression, yet these miRNAs were identified in single studies only ( 36 , 37 , 43 , 44 , 48 , 50 , 57 , 59 , 69 , 71 , 74 , 76 , 77 , 80 , 81 ).…”

Section: Qualitative Synthesis Of Studiesmentioning

confidence: 99%

A Big Role for microRNAs in Gestational Diabetes Mellitus

et al. 2022

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Maternal diabetes is associated with pregnancy complications and poses a serious health risk to both mother and child. Growing evidence suggests that pregnancy complications are more frequent and severe in pregnant women with pregestational type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) compared to women with gestational diabetes mellitus (GDM). Elucidating the pathophysiological mechanisms that underlie the different types of maternal diabetes may lead to targeted strategies to prevent or reduce pregnancy complications. In recent years, microRNAs (miRNAs), one of the most common epigenetic mechanisms, have emerged as key players in the pathophysiology of pregnancy-related disorders including diabetes. This review aims to provide an update on the status of miRNA profiling in pregnancies complicated by maternal diabetes. Four databases, Pubmed, Web of Science, EBSCOhost, and Scopus were searched to identify studies that profiled miRNAs during maternal diabetes. A total of 1800 articles were identified, of which 53 are included in this review. All studies profiled miRNAs during GDM, with no studies on miRNA profiling during pregestational T1DM and T2DM identified. Studies on GDM were mainly focused on the potential of miRNAs to serve as predictive or diagnostic biomarkers. This review highlights the lack of miRNA profiling in pregnancies complicated by T1DM and T2DM and identifies the need for miRNA profiling in all types of maternal diabetes. Such studies could contribute to our understanding of the mechanisms that link maternal diabetes type with pregnancy complications.

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“…MiR‐4691‐3p is one of the understudied microRNAs with unknown function. MiR‐4691‐3p downregulation has been linked to diabetes (Hu et al, 2021; Vasu et al, 2019), whereas its upregulation has been linked to obesity (Hubal et al, 2017; Zhang et al, 2019). A recent study suggests that miR‐4691‐3p preferentially targets the SARS‐CoV‐2 genome (Pathak & Mishra, 2021).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐4691‐3p inhibits the inflammatory response by targeting STING in human dental pulp cells: A laboratory investigation

et al. 2023

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AimThe regulation of human dental pulp inflammation is not fully understood. This study aims to investigate the effect of miR‐4691‐3p on the cGAS‐STING signaling cascade and its downstream cytokines production in human dental pulp cells (HDPCs)MethodologyNormal dental pulp tissue and pulp tissue with irreversible pulpitis from third molars were collected. HDPCswere isolated from pulp tissue. The expression of STING mRNA and miR‐4691‐3p was measured by quantitative real‐time PCR (qRT‐PCR). Bioinformatic computation via TargetScanHuman 8.0 and a luciferase reporter assay was used to identify the targets of miR‐4691‐3p. A miR‐4691‐3p mimic and inhibitor were used to upregulate or downregulate miR‐4691‐3p expression in HDPCs. HDPCs were transfected with c‐di‐AMP, c‐di‐GMP, cGAMP, interferon stimulatory DNA (ISD), bacterial genomic DNA. Immunoblot was performed to detect the phosphorylation of TBK1, p65, and IRF3. Enzyme‐linked immunoassay (ELISA) was performed to detect the cytokines including IFN‐β, TNF, or IL‐6 downstream of cGAS‐STING.ResultsMiR‐4691‐3p expression was increased in human dental pulp tissue with irreversible pulpitis. Treatment of HDPCs using recombinant human IFN‐β, TNF, or IL‐6 also upregulated miR‐4691‐3p. The bioinformatic prediction and luciferase reporter assay confirmed that STING was a direct target of miR‐4691‐3p. The miR‐4691‐3p mimic suppressedSTING expression, the phosphorylation of TBK1, p65, and IRF3, and the IFN‐β, TNF, or IL‐6 production. In contrast, the miR‐4691‐3p inhibitor enhanced the STING expression, the phosphorylation of TBK1, p65, and IRF3, and the IFN‐β, TNF, or IL‐6 production.ConclusionsMiR‐4691‐3p negatively regulates the cGAS‐STING pathway by directly targeting STING. This provides insight to utilize miRNA‐dependent regulatory effect to treat endodontic disease as well as STING‐dependent systemic inflammatory disease.

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Diagnostic value of candidate noncoding RNAs in leukocytes of patients with gestational diabetes mellitus

Cited by 7 publications

References 32 publications

The transcriptomic and epigenetic alterations in type 2 diabetes mellitus patients of Chinese Tibetan and Han populations

The transcriptomic and epigenetic alterations in type 2 diabetes mellitus patients of Chinese Tibetan and Han populations

A Big Role for microRNAs in Gestational Diabetes Mellitus

MicroRNA‐4691‐3p inhibits the inflammatory response by targeting STING in human dental pulp cells: A laboratory investigation

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