Epigenetic alternations of microRNAs and DNA methylation contribute to gestational diabetes mellitus

Zhu, Weiqiang; Shen, Yuxia; Liu, Junwei; Fei, Xiaoping; Zhang, Zhaofeng; Li, Min; Chen, Xiaohong; Xu, Jianhua; Zhu, Qianxi; Zhou, Weijin; Zhang, Meihua; Liu, Shangqing; Du, Jing

doi:10.1111/jcmm.15984

Cited by 35 publications

(21 citation statements)

References 51 publications

(102 reference statements)

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“…MicroRNAs (miRNAs) are factors that regulate biological functions and participate in biological processes such as cell division, proliferation, differentiation, and development. Recent studies have shown that miRNAs are also involved in the regulation of adipocyte differentiation, glucose and lipid metabolism, energy homeostasis, and insulin production and secretion, suggesting that such small nucleic acid molecules may be involved in the pathogenesis of metabolic diseases such as obesity and diabetes [ 20 ]. The expression of miRNA-143 in the placenta tissue of patients with gestational diabetes increased, suggesting that miRNA-143 may be related to the pathogenesis of patients with gestational diabetes and that exercise can reduce the expression of miRNA-143 in patients with gestational diabetes and help reduce blood sugar in patients with gestational diabetes [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…The insulin was administered via subcutaneous injection, which ensures the effectiveness of the drug as well as potency duration. Notably, in terms of pregnancy outcome and neonatal complications, the combined therapy also outperformed the monotherapy because the reason can be that insulin aspart plus exercise therapy improves the patient's systemic blood circulation, reduces insulin resistance, controls the body's blood sugar, and minimizes the impact on pregnant women and fetuses, thus reducing the incidence of complications during pregnancy [ 20 ]. It further indicates that the combination therapy benefits the control of gestational diabetes mellitus and contributes to a lower incidence of pediatric complications.…”

Section: Discussionmentioning

confidence: 99%

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Insulin Aspart Combined with Exercise Therapy in Spleen Deficiency Type Gestational Diabetes Mellitus: The Effect on Disease Control and Pregnancy Outcomes

Shi

Meng

2022

Evidence-Based Complementary and Alternative Medicine

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Objective. To investigate the effect of insulin aspart combined with exercise therapy on the disease control and pregnancy outcomes of spleen deficiency type gestational diabetes mellitus patients. Methods. In this prospective study, a total of 102 patients with spleen deficiency type gestational diabetes mellitus admitted to our hospital from January 2019 to December 2019 were selected and assigned at a ratio of 1 : 1 via the random number table method to receive insulin aspart (control group) or insulin aspart plus exercise therapy (observation group). Outcome measures include blood sugar, clinical efficacy, adverse pregnancy outcomes, and complications. Results. Insulin aspart plus exercise therapy was associated with significantly lower blood glucose and glycosylated hemoglobin levels versus insulin aspart alone ( P < 0.05 ). Insulin aspart plus exercise therapy resulted in significantly higher total efficacy (96.08%) versus insulin aspart (74.51%) ( P < 0.05 ). Patients receiving insulin aspart plus exercise therapy showed a significantly lower incidence of adverse pregnancy outcomes (3.92%) versus those given insulin aspart alone (37.25%) ( P < 0.05 ). Insulin aspart plus exercise therapy resulted in a lower incidence of complications (5.88%) versus insulin aspart (41.17%) ( P < 0.05 ). Conclusion. Exercise therapy plus insulin aspart might offer a viable treatment alternative for patients with spleen deficiency-type gestational diabetes mellitus given its promising effects in disease control and pregnancy outcomes, with good efficacy and safety profiles.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Insulin Aspart Combined with Exercise Therapy in Spleen Deficiency Type Gestational Diabetes Mellitus: The Effect on Disease Control and Pregnancy Outcomes

Shi

Meng

2022

Evidence-Based Complementary and Alternative Medicine

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“…Therefore, SAM must be constantly produced to maintain SAM-to-SAH ratios sufficient to support methyltransferase activity ( Clarke, 2006 ; Krijt et al, 2009 ; Walsh et al, 2018 ). Too much or too little methylation of substrates by SAM has been associated with cancer, diabetes, along with other diseases ( Gharipour et al, 2020 ; McMahon et al, 2017 ; Zhu et al, 2020 ). Therefore, intracellular SAM levels are tightly controlled to maintain homeostasis, with loss of regulation resulting in cellular dysfunction ( Gao et al, 2019 ; Lio and Huang, 2020 ; Ouyang et al, 2020 ; Parkhitko et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

SAM homeostasis is regulated by CFIm-mediated splicing of MAT2A

Scarborough

Flaherty

Hunter

et al. 2021

eLife

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S-adenosylmethionine (SAM) is the methyl donor for nearly all cellular methylation events. Cells regulate intracellular SAM levels through intron detention of MAT2A, the only SAM synthetase expressed in most cells. The N6-adenosine methyltransferase METTL16 promotes splicing of the MAT2A detained intron by an unknown mechanism. Using an unbiased CRISPR knock-out screen, we identified CFIm25 (NUDT21) as a regulator of MAT2A intron detention and intracellular SAM levels. CFIm25 is a component of the cleavage factor Im (CFIm) complex that regulates poly(A) site selection, but we show it promotes MAT2A splicing independent of poly(A) site selection. CFIm25-mediated MAT2A splicing induction requires the RS domains of its binding partners, CFIm68 and CFIm59 as well as binding sites in the detained intron and 3´ UTR. These studies uncover mechanisms that regulate MAT2A intron detention and reveal a previously undescribed role for CFIm in splicing and SAM metabolism.

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“…The matrix files of the above three data sets were downloaded and the R language limma package was utilized to screen out deferentially expressed genes (DEGs), miRNAs (DEMs), and methylated CpG probes (DMPs) (W. Zhu W. et al, 2020 ). Subsequently, DEGs, DEMs, and DMPs were filtered out, using p <0.05 and abs (t) > 2 as cutoff values.…”

Section: Methodsmentioning

confidence: 99%

Epigenetic Biomarkers Screening of Non-Coding RNA and DNA Methylation Based on Peripheral Blood Monocytes in Smokers

Huang

Zhang

et al. 2022

Front. Genet.

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This study aims to use bioinformatics methods to determine the epigenetic changes in microRNA expression and DNA methylation caused by cigarette smoking. The data of mRNA, miRNA expression, and methylation microarray were obtained from the GEO database to filter differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and methylated CpG probes (DMPs) through the limma package. The R clusterProfile package was used for functional annotation and enrichment analysis. The protein-protein interaction (PPI) network was constructed by the String database and visualized in Cytoscape software. Starbase database was employed to predict lncRNA and CirRNA based on the sequence of miRNA, and to establish a regulatory network of ceRNA. By overlapping DEG and DEM, 107 down-miRNA-targeted up-regulated genes and 65 up-miRNA-target down-regulated genes were obtained, which were mainly enriched in autophagy signaling pathways and protein ubiquitination pathways, respectively. In addition, 324 genes with low methylation and high expression and 204 genes with high methylation and low expression were respectively related to the degeneration of the nervous system and the function of the cardiovascular system. Interestingly, 43 genes were up-regulated under the dual regulation of reduced miRNA and hypomethylation, while 14 genes were down-regulated under the dual regulation of increased miRNA and hypermethylation. Ten chemicals have been identified as putative therapeutic agents for pathological conditions caused by smoking. In addition, among these genes, HSPA4, GRB2, PRKCA, and BCL2L1 could play a fundamental role in related diseases caused by smoking and may be used as the biomarkers for precise diagnosis and targets for future therapies of smoking-related diseases.

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Epigenetic alternations of microRNAs and DNA methylation contribute to gestational diabetes mellitus

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 35 publications

References 51 publications

Insulin Aspart Combined with Exercise Therapy in Spleen Deficiency Type Gestational Diabetes Mellitus: The Effect on Disease Control and Pregnancy Outcomes

Insulin Aspart Combined with Exercise Therapy in Spleen Deficiency Type Gestational Diabetes Mellitus: The Effect on Disease Control and Pregnancy Outcomes

SAM homeostasis is regulated by CFIm-mediated splicing of MAT2A

Epigenetic Biomarkers Screening of Non-Coding RNA and DNA Methylation Based on Peripheral Blood Monocytes in Smokers

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