miR-17-5p Promotes Glucose Uptake of HTR8/SVneo Trophoblast Cells by Inhibiting TXNIP/NLRP3 Inflammasome Pathway

Jiang, Yi; Wei, Lijie; Zhang, Huiting; Chen, Yuting; Gao, Peng; Zhang, Jingyi; Zhou, Xuan; Zhu, Sicong; Du, Yuanyuan; Fang, Chenyun; Li, Jiaqi; Li, Feng; He, Mengzhou; Wang, Shaoshuai; Yu, Jun

doi:10.2147/dmso.s385774

Cited by 9 publications

(6 citation statements)

References 39 publications

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“…Cyanidin-3-O-glucoside protects endothelial cells by regulating the miR-204-5p/SIRT1-mediated inflammatory response and apoptosis ( Wang Z. et al, 2020 ). MiR-17-5p inhibits the TXNIP/NLRP3 inflammatory pathway and promotes glucose uptake in HTR8/SVneo trophoblast cells ( Jiang et al, 2022 ). Downregulation of miR-17-5p alleviates apoptosis and fibrosis in human renal interstitial cells induced by high glucose ( Chen et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of common genes and pathways between type 2 diabetes and COVID-19

Wang,

Li,

et al. 2024

Front. Genet.

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Background:Numerous studies have reported a high incidence and risk of severe illness due to coronavirus disease 2019 (COVID-19) in patients with type 2 diabetes (T2DM). COVID-19 patients may experience elevated or decreased blood sugar levels and may even develop diabetes. However, the molecular mechanisms linking these two diseases remain unclear. This study aimed to identify the common genes and pathways between T2DM and COVID-19.Methods:Two public datasets from the Gene Expression Omnibus (GEO) database (GSE95849 and GSE164805) were analyzed to identify differentially expressed genes (DEGs) in blood between people with and without T2DM and COVID-19. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the common DEGs. A protein-protein interaction (PPI) network was constructed to identify common genes, and their diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analysis. Validation was performed on the GSE213313 and GSE15932 datasets. A gene co-expression network was constructed using the GeneMANIA database to explore interactions among core DEGs and their co-expressed genes. Finally, a microRNA (miRNA)-transcription factor (TF)-messenger RNA (mRNA) regulatory network was constructed based on the common feature genes.Results:In the GSE95849 and GSE164805 datasets, 81 upregulated genes and 140 downregulated genes were identified. GO and KEGG enrichment analyses revealed that these DEGs were closely related to the negative regulation of phosphate metabolic processes, the positive regulation of mitotic nuclear division, T-cell co-stimulation, and lymphocyte co-stimulation. Four upregulated common genes (DHX15, USP14, COPS3, TYK2) and one downregulated common feature gene (RIOK2) were identified and showed good diagnostic accuracy for T2DM and COVID-19. The AUC values of DHX15, USP14, COPS3, TYK2, and RIOK2 in T2DM diagnosis were 0.931, 0.917, 0.986, 0.903, and 0.917, respectively. In COVID-19 diagnosis, the AUC values were 0.960, 0.860, 1.0, 0.9, and 0.90, respectively. Validation in the GSE213313 and GSE15932 datasets confirmed these results. The miRNA-TF-mRNA regulatory network showed that TYH2 was targeted by PITX1, PITX2, CRX, NFYA, SREBF1, RELB, NR1L2, and CEBP, whereas miR-124-3p regulates THK2, RIOK2, and USP14.Conclusion:We identified five common feature genes (DHX15, USP14, COPS3, TYK2, and RIOK2) and their co-regulatory pathways between T2DM and COVID-19, which may provide new insights for further molecular mechanism studies.

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Section: Discussionmentioning

confidence: 99%

Identification of common genes and pathways between type 2 diabetes and COVID-19

Wang,

Li,

et al. 2024

Front. Genet.

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“…Yi et al confirmed that TXNIP was increased in placental samples of GDM patients, which was consistent with ours. It is reported that MiR-17-5p could up regulate the expression of TXNIP, improved glucose uptake of HTR-8/Svneo cells by TXNIP/NLRP3 axis [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

High TXNIP expression accelerates the migration and invasion of the GDM placenta trophoblast

Yang

et al. 2023

BMC Pregnancy Childbirth

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Introduction Our previous study has proofed the glucose sensitive gene-thioredoxin-interacting protein (TXNIP) expression was up in the placenta of the patients with gestational diabetes mellitus (GDM), but the pathological mechanisms underlying abnormal TXNIP expression in the placenta of patients with GDM is completely unclear and additional investigations are required to explain the findings we have observed. In the present study, we simulated the high TXNIP expression via introducing the Tet-On “switch” in vitro, approximate to its expression level in the real world, to explore the following consequence of the abnormal TXNIP. Methods The expression and localization of TXNIP in the placenta of GDM patients and the health control was investigated via immunofluorescent staining, western blot and RT-qPCR. Overexpression of TXNIP was achieved through transfecting Tet-on system to the human trophoblastic cell line-HTR-8/Svneo cell. TXNIP knockout was obtained via CRISPR-Cas9 method. The cell phenotype was observed via IncuCyte Imaging System and flow cytometry. The mechanism was explored via western blot and RT-qPCR. Results The expression level of TXNIP in the GDM placenta was nearly 2–3 times higher than that in the control. The TXNIP located at trophoblastic cells of the placenta. When the expression of TXNIP was upregulated, the migration and invasion of the cells accelerated, but cell apoptosis and proliferation did not changed compared with the control group. Furthermore, the size of the TetTXNIP cells became larger, and the expression level of Vimentin and p-STAT3 increased in the TetTXNIP cells. All the changes mentioned above were opposite in the TXNIP-KO cells. Conclusions Abnormal expression of TXNIP might be related to the impairment of the GDM placental function, affecting the migration and invasion of the placental trophoblast cells through STAT3 and Vimentin related pathway; thus, TXNIP might be the potential therapeutic target for repairing the placental dysfunction deficient in GDM patients.

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“…17 Additionally, recent studies reported that inhibiting the TXNIP/NLRP3 inflammasome pathway increased glucose absorption in HTR8/ SVneo trophoblast cells, suggesting that miR-17-5p may be a potential target for reducing insulin resistance and treating DM. 78 The study found that the expression level of KCNQ10OT1 in the serum of diabetic patients was higher than that of healthy individuals in the control group. 85 Thus, the lncRNA-miRNA-mRNA interaction network can be a target for regulating the onset and progression of diabetes.…”

Section: The Mechanism Of Ncrna-regulate Pyroptosis In Diabetesmentioning

confidence: 90%

“…In HG‐treated INS‐1 pancreatic β cells of rats and an HFD/STZ mice model, miR‐17‐5p mimics rescued insulin secretion dysfunction by suppressing the activation of the TXNIP/NLRP3 inflammasome pathway 17 . Additionally, recent studies reported that inhibiting the TXNIP/NLRP3 inflammasome pathway increased glucose absorption in HTR8/SVneo trophoblast cells, suggesting that miR‐17‐5p may be a potential target for reducing insulin resistance and treating DM 78 . The study found that the expression level of KCNQ10OT1 in the serum of diabetic patients was higher than that of healthy individuals in the control group 85 .…”

Section: The Mechanism Of Ncrna‐regulated Pyroptosis In Diabetes and Vcdmentioning

confidence: 99%

The role of ncRNAs‐mediated pyroptosis in diabetes and its vascular complications

Feng,

Yang,

Zhong

et al. 2024

Cell Biochemistry & Function

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Over the past decade, the prevalence of diabetes has increased significantly worldwide, leading to an increase in vascular complications of diabetes (VCD), such as diabetic cardiomyopathy (DCM), diabetic nephropathy (DN), and diabetic retinopathy (DR). Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long Noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), play a key role in cellular processes, including the pathophysiology of diabetes and VCD via pyroptosis. ncRNAs (e.g., miR‐17, lnc‐MEG3, and lnc‐KCNQ1OT1) can regulate pyroptosis in pancreatic β cells. Some ncRNAs are involved in VCD progression. For example, miR‐21, lnc‐KCNQ1OT1, lnc‐GAS5, and lnc‐MALAT1 were reported in DN and DCM, and lnc‐MIAT was identified in DCM and DR. Herein, this review aimed to summarize recent research findings related to ncRNAs‐mediated pyroptosis at the onset and progression of diabetes and VCD.

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miR-17-5p Promotes Glucose Uptake of HTR8/SVneo Trophoblast Cells by Inhibiting TXNIP/NLRP3 Inflammasome Pathway

Cited by 9 publications

References 39 publications

Identification of common genes and pathways between type 2 diabetes and COVID-19

Identification of common genes and pathways between type 2 diabetes and COVID-19

High TXNIP expression accelerates the migration and invasion of the GDM placenta trophoblast

The role of ncRNAs‐mediated pyroptosis in diabetes and its vascular complications

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