NRF2-driven miR-125B1 and miR-29B1 transcriptional regulation controls a novel anti-apoptotic miRNA regulatory network for AML survival

Shah, Niraj M.; Zaitseva, Lyubov; Bowles, Kristian M.; MacEwan, David J.; Rushworth, Stuart A.

doi:10.1038/cdd.2014.152

Cited by 60 publications

(59 citation statements)

References 42 publications

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“…Grin2b could compete with mmu_circRNA_34132 for binding to mmu-miR-29b-1-5p based on this study. Moreover, Nrf2 could downregulate miR-29b-1 through binding to specific ARE sites [53]. These findings suggested that mmu_circRNA_34132-mmu-miR-29b-1-5p-Grin2b interaction might play a role in neurodegenerative diseases that are regulated by Nrf2.…”

Section: Discussionmentioning

confidence: 81%

The Differentially Expressed Circular RNAs in the Substantia Nigra and Corpus Striatum of Nrf2-Knockout Mice

Yang¹,

Zhang²,

Lin³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a protective role in both acute neuronal damage and chronic neurodegeneration-related oxidative stress. Circular RNAs (circRNAs) are involved with various diseases in the central nervous system (CNS). This study aimed to identify the key circRNAs involved in Nrf2-neuroprotection against oxidative stress. Methods: The differentially expressed circRNAs (DEcircRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice were identified by microarray analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was then used to validate the expression of selected DEcircRNAs in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice. Based on our previous microarray analysis of the differentially expressed mRNAs (DEmRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice, the DEcircRNA-miRNA-DEmRNA interaction network was constructed. Functional annotation of DEmRNAs that shared the same binding miRNAs with DEcircRNAs was performed using gene ontology (GO) and pathway analyses. Results: A total of 65 and 150 significant DEcircRNAs were obtained in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, respectively, and seventeen shared DEcircRNAs were found in both these two tissues. The qRT-PCR results were generally consistent with the microarray results. The DEcircRNA-miRNA-DEmRNA interaction network and pathway analysis indicated that mmu_circRNA_34132, mmu_circRNA_017077 and mmu-circRNA-015216 might be involved with Nrf2-mediated neuroprotection against oxidative stress. Mmu_circRNA_015216 and mmu_circRNA_017077 might play roles in the Nrf2-related transcriptional misregulation and Nrf2-mediated processes of rheumatoid arthritis, respectively. In addition to these two processes, mmu_circRNA_34132 may be a potential regulator of Nrf2-mediated protection for diabetes mellitus and Nrf2-mediated defence against ROS in hearts. Conclusion: In conclusion, our study identified the key DEcircRNAs in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, which might provide new clues for further exploring the mechanism of Nrf2-mediated neuroprotection against oxidative stress and other Nrf2-mediated processes.

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Section: Discussionmentioning

confidence: 81%

The Differentially Expressed Circular RNAs in the Substantia Nigra and Corpus Striatum of Nrf2-Knockout Mice

Yang¹,

Zhang²,

Lin³

et al. 2018

Cell Physiol Biochem

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“…NRF2 binds to the sites of antioxidant responsive element (ARE) in the promoters of miR-125B1 and miR-29B1. NRF2 functionally promotes the expression of miR125B1, while NRF2 negatively controls miR-29B1expression2627. We next measured expression of both miR-125B1 and miR-29B1 in these two types of cells.…”

Section: Resultsmentioning

confidence: 99%

ROS-mediated Different Homeostasis of Murine Corneal Epithelial Progenitor Cell Line under Oxidative Stress

Zhou

Jia

et al. 2016

Sci Rep

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The role of ROS in stem cell biology has not been fully illustrated and understood. Here we compared the different responses and investigated the mechanism underlying oxidative stress induced by hydrogen peroxide (H2O2) between murine corneal epithelial progenitor cell line (TKE2) and mature murine corneal epithelial cells (MCE). TKE2 showed a different homeostasis and strong resistance to H2O2. TKE2 reduced the production of ROS, inhibited ROS generation enzyme NADPH oxidase 4 (NOX4), and increased dual specificity phosphatase 6 (DUSP6). Furthermore, TKE2 activated nuclear factor (erythroid-derived 2)-like 2 (NRF2) signaling pathway, regulated miR-125B1 and miR-29B1, and elevated levels of antioxidants glutathione S-transferase P (GSTP) and superoxide dismutases (SOD). The association with ROS of the cells was also verified by RNA interference approach and pharmacological antagonization. In addition, TKE2 enhanced the autophagy after exposure to H2O2. The novel evidence suggests that TKE2 cells have different homeostasis and strong antioxidant properties against oxidative stress via the regulation of ROS formation and pathway.

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“…In acute myeloid leukaemia, a study showed that by decreasing the expression of miR-125B and increasing the expression of miR-29B, the cells showed increased sensitivity to apoptotic stimuli. 29 miR-125b-5p regulates GSH levels and hence acetaminophen-induced ALF by modulation of the Keap1-Nrf2 signalling pathway. However, Nrf2 may also contribute to further changes in miR-125b levels via a feedback loop as reported previously.…”

Section: Group (N = 3) Nrf2 Mir-125bmentioning

confidence: 99%

The expression of miR‐125b in Nrf2‐silenced A549 cells exposed to hyperoxia and its relationship with apoptosis

Zhang

Chu

Gong

et al. 2019

J Cellular Molecular Medi

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Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects the quality of life of infants. At present, premature exposure to hyperoxia for extended periods of time is believed to affect the development of lung tissue and vascularity, resulting in BPD. The oxidative stress caused by hyperoxia exposure is an important risk factor for BPD in premature infants. Nuclear factor E2‐related factor 2 (Nrf2) is an important regulator of antioxidant mechanisms. As a microRNA, microRNA‐125b (miR‐125b) plays an important role in cell proliferation, differentiation and apoptosis. Although the Nrf2/ARE pathway has been extensively studied, little is known about the regulatory role of microRNAs in Nrf2 expression. In this study, the expression levels of Nrf2 and miR‐125b in the lung tissues of premature Sprague Dawley (SD) rats and A549 cells exposed to hyperoxia were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR), and the apoptosis of A549 cells was detected by flow cytometry. The results showed that Nrf2 and miRNA‐125b in the lung tissues of premature rats increased significantly upon exposure to hyperoxia and played a protective role. Nrf2 was suppressed by small interfering RNA (siRNA) in A549 cells, miR‐125b was similarly inhibited, and apoptosis was significantly increased. These results suggest that miR‐125b helps protect against BPD as a downstream target of Nrf2.

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NRF2-driven miR-125B1 and miR-29B1 transcriptional regulation controls a novel anti-apoptotic miRNA regulatory network for AML survival

Cited by 60 publications

References 42 publications

The Differentially Expressed Circular RNAs in the Substantia Nigra and Corpus Striatum of Nrf2-Knockout Mice

The Differentially Expressed Circular RNAs in the Substantia Nigra and Corpus Striatum of Nrf2-Knockout Mice

ROS-mediated Different Homeostasis of Murine Corneal Epithelial Progenitor Cell Line under Oxidative Stress

The expression of miR‐125b in Nrf2‐silenced A549 cells exposed to hyperoxia and its relationship with apoptosis

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