miR‑29b affects neurocyte apoptosis by targeting MCL‑1 during cerebral ischemia/reperfusion injury

Huang, Zhi; Lu, Lu; Jiang, Tianyan; Zhang, Shuai; Shen, Yulong; Zheng, Zhu; Zhao, Ansu; Gao, Rui; Li, Rui; Zhou, Shi; Liu, Jing

doi:10.3892/etm.2018.6622

Cited by 15 publications

(13 citation statements)

References 22 publications

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“…Previous studies revealed that dysregulation of miR-29 family promoted cell apoptosis in many human diseases including cerebral ischemia/reperfusion injury, pulmonary arterial hypertension, and myocarditis (Chen et al, 2018;Huang et al, 2018;Zhang et al, 2018). Yuan et al (2018) found that miR-29b would activate NF-κB, thus aggravating endothelial cell inflammatory damage.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-29b-3p Promotes Human Retinal Microvascular Endothelial Cell Apoptosis via Blocking SIRT1 in Diabetic Retinopathy

Yong

Cui²,

Liu³

et al. 2020

Front. Physiol.

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Background: Diabetic retinopathy (DR) is a main complication of diabetes mellitus (DM). Recent studies have implicated microRNAs in human retinal microvascular endothelial cell (HRMEC) dysfunction. In this study, we aim to investigate the apoptotic promotion of miR-29b-3p by blocking SIRT1 in HRMEC for DR situation. Method: Blood samples were obtained from DR patients and controls. Dual-luciferase reporter assay using HEK-293T cells was performed to show the direct interaction of miR-29b-3p and the 3 UTR of SIRT1. HRMECs were exposed to 5.5 mmol/L of glucose (normal control), 5.5 mmol/L of glucose and 24.5 mmol/L of mannitol (osmotic pressure control), 30 mmol/L of glucose [hyperglycemia (HG)], 150 µmol/L of CoCl 2 (hypoxia), and 30 mmol/L of glucose plus 150 µmol/L of CoCl 2 (HG-CoCl 2). To identify the regulating relationship between miR-29b-3p and SIRT1, HRMECs were transfected with miR-29b-3p mimics/inhibitors or their negative controls. SRT1720 was used as a SIRT1 agonist. Cell viability was assessed with the cell counting kit-8 (CCK-8) assay, and apoptotic cells were stained by one-step terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay kit. Gene and protein expression were assayed by quantitative real-time reverse transcriptase-PCR (RT-qPCR) and western blotting separately. Result: MiR-29b-3p was upregulated to 3.2-fold, and SIRT1 protein was downregulated to 65% in DR patients. Dual-luciferase reporter assay showed the direct interaction of miR-29b-3p and SIRT1. HRMECs were identified as >95% positive for CD31 and von Willebrand factor (vWF). MiR-29b-3p and Bax/Bcl-2 ratio was upregulated, whereas SIRT1 was downregulated in HRMECs in the HG-CoCl 2 condition. Decreased cell viability and upregulated apoptosis were also found in HRMECs of the HG-CoCl 2 condition. Upregulated miR-29b-3p decreased the expression of SIRT1 and increased the ratio of Bax/Bcl-2, whereas downregulated miR-29b-3p increased the expression of SIRT1 protein and downregulated the ratio of

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Section: Discussionmentioning

confidence: 99%

MicroRNA-29b-3p Promotes Human Retinal Microvascular Endothelial Cell Apoptosis via Blocking SIRT1 in Diabetic Retinopathy

Yong

Cui²,

Liu³

et al. 2020

Front. Physiol.

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“…In spite of that, there are data indicating a rather proapoptotic nature of miR-29b-3p . Namely, miR-29b-3p has been described to alter BH3-only protein levels in favor of neuronal degeneration [76,84]. In addition, miR-29 has an activating effect on the proapoptotic factor p53 [136], which was found to be elevated in both ALS patients and the wobbler mouse [137,138].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, miR-29b-3p also binds mRNA from antiapoptotic factors, such as Mcl1, providing a more proapoptotic effect. Mcl1, a member of the Bcl2 family, binds proapoptotic factors such as Bak, BIM, or PUMA and thus prevents the initiation of apoptotic cell death [84,85,86]. Since miR29b-3p regulates both, pro- and antiapoptotic proteins (e.g., Bax, Mcl1 or BMF), it is not clear whether deregulation of this miRNA exerts protective or destructive functions [84,87].…”

Section: Introductionmentioning

confidence: 99%

Deregulated miR-29b-3p Correlates with Tissue-Specific Activation of Intrinsic Apoptosis in An Animal Model of Amyotrophic Lateral Sclerosis

Klatt

Theis

Hahn

et al. 2019

Cells

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Amyotrophic lateral sclerosis (ALS) is one of the most common incurable motor neuron disorders in adults. The majority of all ALS cases occur sporadically (sALS). Symptoms of ALS are caused by a progressive degeneration of motor neurons located in the motor cortex and spinal cord. The question arises why motor neurons selectively degenerate in ALS, while other cells and systems appear to be spared the disease. Members of the intrinsic apoptotic pathway are frequent targets of altered microRNA expression. Therefore, microRNAs and their effects on cell survival are subject of controversial debates. In this study, we investigated the expression of numerous members of the intrinsic apoptotic cascade by qPCR, western blot, and immunostaining in two different regions of the CNS of wobbler mice. Further we addressed the expression of miR-29b-3p targeting BMF, Bax, and, Bak, members of the apoptotic pathway. We show a tissue-specific differential expression of BMF, Bax, and cleaved-Caspase 3 in wobbler mice. An opposing regulation of miR-29b-3p expression in the cerebellum and cervical spinal cord of wobbler mice suggests different mechanisms regulating the intrinsic apoptotic pathway. Based on our findings, it could be speculated that miR-29b-3p might regulate antiapoptotic survival mechanisms in CNS areas that are not affected by neurodegeneration in the wobbler mouse ALS model.

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“…The expression of miR-29b has been demonstrated to show significant upregulation, not only in the brains of MCAO rats, but also in neurons and astrocytes exposed to oxygen and glucose deprivation (OGD). Furthermore, miR-29b was revealed to up-regulate the expression of myeloid cell leukemia-1 (MCL-1) and B-cell lymphoma 2 (BCL-2) proteins following down-regulation of caspase-3 expression in a cerebral I/R injury cell model, which was confirmed to result from the regulation of the Akt signaling pathway by miR-29b (25)(26)(27)(28). Additionally, it has been confirmed that repression of BCL-2 or Bcl2L2 gene occurred after the upregulation of miR-29b, which subsequently resulted in the promotion of neuronal cell death (27,29).…”

Section: Discussionmentioning

confidence: 95%

Analysis of microRNA expression in cerebral ischemia/reperfusion after mild therapeutic hypothermia treatment in rats

Zhao¹,

Liu²,

Kang³

et al. 2021

Ann Transl Med

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Background: This study aimed to explore the molecular mechanism of mild hypothermia in in the treatment of cerebral ischemia, microRNA (miRNA) microarrays and bioinformatics analysis were employed to examine the miRNA expression profiles of rats with mild therapeutic hypothermia after middle cerebral artery occlusion (MCAO).Methods: MCAO was induced in Male Sprague-Dawley rats. Mild hypothermia treatment began from the onset of ischemia and maintained for 3 hours. miRNA expressions following focal cerebral ischemia and mild hypothermia treatment were profiled using microarray technology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the functions of the target genes in mild therapeutic hypothermia after MCAO. 60 min before MCAO, mimics and inhibitor of miR-291b were injected into the right lateral ventricle respectively, then the infarct volume and neuronal apoptosis were analyzed.Results: Six upregulated miRNAs and 6 downregulated miRNAs were detected 4 hours after mild therapeutic hypothermia, and after 24 hours, 41 and 10 miRNAs were upregulated and downregulated, respectively. The target genes of the differentially expressed genes were mainly related with multicellular organism development and the mucin type O-glycan biosynthesis pathway was the most enriched KEGG pathway. Among the differentially expressed miRNAs, miR-291b was selected to assess the effects of mild therapeutic hypothermia in MCAO rats. At 24 hours after mild therapeutic hypothermia, miR-291b overexpression was proved to exhibit neuroprotective effects. Conclusions:The results showed that miRNAs might play a pivotal role in mild therapeutic hypothermia in cerebral ischemia/reperfusion injury. Further understanding of the mechanism and function of miRNAs would help to illuminate the mechanism of mild therapeutic hypothermia in cerebral ischemia/reperfusion injury.

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miR‑29b affects neurocyte apoptosis by targeting MCL‑1 during cerebral ischemia/reperfusion injury

Cited by 15 publications

References 22 publications

MicroRNA-29b-3p Promotes Human Retinal Microvascular Endothelial Cell Apoptosis via Blocking SIRT1 in Diabetic Retinopathy

MicroRNA-29b-3p Promotes Human Retinal Microvascular Endothelial Cell Apoptosis via Blocking SIRT1 in Diabetic Retinopathy

Deregulated miR-29b-3p Correlates with Tissue-Specific Activation of Intrinsic Apoptosis in An Animal Model of Amyotrophic Lateral Sclerosis

Analysis of microRNA expression in cerebral ischemia/reperfusion after mild therapeutic hypothermia treatment in rats

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