RETRACTED ARTICLE: Up-regulated microRNA-199b-3p represses the apoptosis of cerebral microvascular endothelial cells in ischemic stroke through down-regulation of MAPK/ERK/EGR1 axis

Yong, Ya-Xiong; Yang, Hua; Lian, Jia; Xu, Xiaowei; Han, Ke; Hu, Ming‐yi; Wang, Huacheng; Zhou, Liemin

doi:10.1080/15384101.2019.1632133

Cited by 34 publications

(23 citation statements)

References 44 publications

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“…In addition to cancer, hsa-miR-199b-3p plays an important role in other diseases. The apoptosis of cerebral microvascular endothelial cells was repressed via upregulation of hsa-miR-199b-3p in ischemic stroke [ 28 ]. Wu et al showed that hsa-miR-199b-3p was substantially increased in extracellular vesicles from the nasal mucus of patients with allergic rhinitis [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

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hsa‐miR‐199b‐3p Prevents the Epithelial‐Mesenchymal Transition and Dysfunction of the Renal Tubule by Regulating E‐cadherin through Targeting KDM6A in Diabetic Nephropathy

Bai

Xiong

Tang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. The association between epithelial-mesenchymal transition (EMT) and fibrosis is quite ascertained, but its link to eventual tubule dysfunction is missing. Here, we show that human microRNA- (hsa-miR-) 199b-3p protects renal tubules from diabetic-induced injury by repressing KDM6A, a histone lysine demethylase regulating E-cadherin expression. Lower E-cadherin expression is related to a higher level of KDM6A, while E-cadherin is promoted upon treatment with the KDM6A inhibitor GSK-J4 in both high glucose- (HG-) induced HK2 cells and the kidneys from streptozotocin- (STZ-) induced type 1 diabetic mice. However, overexpression or RNA silencing of E-cadherin fails to alter KDM6A expression. We also show that the upregulation of KDM6A is associated with the increased methylation level of the E-cadherin promoter. Then, the target prediction results and a dual-luciferase assay show that hsa-miR-199b-3p is a new miRNA that targets KDM6A. Overexpression of hsa-miR-199b-3p increases E-cadherin expression and prevents EMT through repressing KDM6A expression in HG-induced HK2 cells. In contrast, inhibitor-induced hsa-miR-199b-3p knockdown has opposite effects, as it decreases E-cadherin level and worsens EMT, accompanied by increased levels of KDM6A. Besides, Mir199b-knockout mice without mmu-miR-119b-3p expression exhibit more renal tubule dysfunction and more serious kidney tissue damage upon treatment with STZ. These results demonstrate that hsa-miR-199b-3p improves E-cadherin expression and prevents the progression of DN through targeting KDM6A. miR-199b-3p could be a future biomarker or target for the diagnosis or treatment of DN.

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Section: Discussionmentioning

confidence: 99%

“…PCR quantification was performed as previously described [ 26 ]. To test miRNA expression, we used stem-loop qRT-PCR for miR-199a-3p, miR-199b-3p, and miR-758-3p following the protocol described previously [ 27 , 28 ]. Primers are shown in Table S2 .…”

Section: Methodsmentioning

confidence: 99%

hsa‐miR‐199b‐3p Prevents the Epithelial‐Mesenchymal Transition and Dysfunction of the Renal Tubule by Regulating E‐cadherin through Targeting KDM6A in Diabetic Nephropathy

Bai

Xiong

Tang

et al. 2021

Oxidative Medicine and Cellular Longevity

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show abstract

“…MiRNA-210 induces the apoptosis of neuronal cells of mouse model with cerebral ischemia by activating the HIF-1α-VEGF pathway [ 25 ]. Upregulation of miRNA-199b-3p effectively suppresses the apoptosis of cerebral microvascular endothelial cells in ischemic stroke by modulating the MAPK/ERK/EGR1 axis [ 26 ]. These evidences all demonstrates that miRNAs are closely involved in the development of ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of miR-20b Protects Against Cerebral Ischemic Stroke by Targeting Thioredoxin Interacting Protein (TXNIP)

Yang

et al. 2021

Exp Neurobiol

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Dysregulation of microRNAs (miRNAs) is involved in abnormal development and pathophysiology in the brain. Although miR-20b plays essential roles in various human diseases, its function in cerebral ischemic stroke remains unclear. A cell model of oxygen glucose deprivation/reoxygenation (OGD/R) and A rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) were constructed. qRT-PCR and western blot were used to evaluate the expression of miR-20b and TXNIP. Cell viability was detected by MTT assay, and cell apoptosis was evaluated by flow cytometry. Targetscan and Starbase were used to predict the potential targets of miR-20b. Luciferase reporter assay was applied to determine the interaction between miR-20b and TXNIP. Rescue experiments were conducted to confirm the functions of miR-20b/TXNIP axis in cerebral ischemic stroke. MiR-20b was significantly downregulated after I/R both in vitro and in vivo. Upregulation of miR-20b inhibited OGD/R-induced neurons apoptosis and attenuated ischemic brain injury in rat model. Bioinformatic prediction suggested that TXNIP might be a target of miR-20b, and luciferase reporter assay revealed that miR-20b negatively regulated TXNIP expression by directly binding to the 3'-UTR of TXNIP. Downregulation of TXNIP inhibited OGD/R-induced neurons apoptosis in vitro and ischemic brain injury in vivo. Rescue experiments indicated that downregulation of TXNIP effectively reversed the effect of miR-20b inhibitor in neurons apoptosis after OGD/R-treatment and ischemic brain injury in a mouse model after MCAO/R-treatment. Our study demonstrated that upregulation of miR-20b protected the brain from ischemic brain injury by targeting TXNIP, extending our understanding of miRNAs in cerebral ischemic stroke.

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“…qPCR quantification was performed by using the TB Green® Fast qPCR Mix (TaKaRa) according to the manufacturer's manual on the ABI-7500 (Applied Biosystems). For testing miRNA expression, stem-loop qRT-PCR was used referring to others' work [ 23 , 24 ]. Primers are shown in Table S1 .…”

Section: Methodsmentioning

confidence: 99%

KDM1A Promotes Immunosuppression in Hepatocellular Carcinoma by Regulating PD-L1 through Demethylating MEF2D

Wang

Cao

2021

Journal of Immunology Research

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Background. Immune checkpoint inhibitor therapy targeting antiprogrammed cell death-1 (anti-PD-1) or its ligand (anti-PD-L1) is effective in the treatment of some hepatocellular carcinomas (HCC). Hence, further identification of biological targets related to PD-L1 regulation in HCC is beneficial to improve the clinical efficacy of immunotherapy. Some HCC cells express lysine-specific demethylase 1A (KDM1A), which is implicated in the reduced survival time of patients. Here, we studied whether the level of PD-L1 and the immunosuppression are regulated by KDM1A and its miRNA in HCC cells. Methods. In the present study, we studied clinical data from The Cancer Genome Atlas (TCGA) database. We performed qPCR and western blotting assays to measure the expression level of genes of interest. PD-L1 expression was also analyzed by FACS. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 was used to generate gene knockout cells to investigate the relationships of genes of interest. We also developed a reporter gene assay (RGA) to explore the changes in T cell-induced antitumor immunity relative to PD-L1 expression in HCC cells. The binding between proteins and promoters or miRNAs and their target genes was explored by luciferase reporter assays. Results. The results showed that PD-L1 and KDM1A were increased in HCC patients and cells, and KDM1A promoted the expression of PD-L1 in HCC cells. Our findings showed that the enhancement of PD-L1 expression was not attributed to mitochondrial dysfunction caused by increases in KDM1A in HCC cells. Furthermore, we observed a lower level of MEF2D methylation in HCC cells than in normal human liver cells. Demethylated MEF2D could bind to the promoter of PD-L1 and activate its expression, while KDM1A interacted with MEF2D and acted as a demethylase to reduce its methylation. Moreover, a new miRNA, miR-329-3p, targeting KDM1A was found to regulate the PD-L1 expression profile in HCC cells. In the xenograft model, the tumors treated with miR-329-3p showed growth inhibition. Conclusions. Mechanistically, miR-329-3p inhibits tumor cellular immunosuppression and reinforces the response of tumor cells to T cell-induced cytotoxic effect by targeting KDM1A mRNA and downregulating its expression, which contributed to MEF2D demethylation and activation of PD-L1 expression.

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RETRACTED ARTICLE: Up-regulated microRNA-199b-3p represses the apoptosis of cerebral microvascular endothelial cells in ischemic stroke through down-regulation of MAPK/ERK/EGR1 axis

Cited by 34 publications

References 44 publications

hsa‐miR‐199b‐3p Prevents the Epithelial‐Mesenchymal Transition and Dysfunction of the Renal Tubule by Regulating E‐cadherin through Targeting KDM6A in Diabetic Nephropathy

hsa‐miR‐199b‐3p Prevents the Epithelial‐Mesenchymal Transition and Dysfunction of the Renal Tubule by Regulating E‐cadherin through Targeting KDM6A in Diabetic Nephropathy

Upregulation of miR-20b Protects Against Cerebral Ischemic Stroke by Targeting Thioredoxin Interacting Protein (TXNIP)

KDM1A Promotes Immunosuppression in Hepatocellular Carcinoma by Regulating PD-L1 through Demethylating MEF2D

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