miR-125b transcriptionally increased by Nrf2 inhibits AhR repressor, which protects kidney from cisplatin-induced injury

Joo, Min Sung; Lee, C G; Koo, Ja Hyun; Kim, S G

doi:10.1038/cddis.2013.427

Cited by 86 publications

(71 citation statements)

References 59 publications

(82 reference statements)

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“…Indeed, recent data showed that miRNAs that are downregulated in tumour cells with hyperactive NRF2 affect the metabolism of these cells 49 and that Nrf2-mediated upregulation of miR-125b suppresses expression of the aryl hydrocarbon receptor in the kidney 15 .…”

Section: Discussionmentioning

confidence: 99%

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A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes

et al. 2014

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The Nrf2 transcription factor controls the expression of genes involved in the antioxidant defense system. Here, we identified Nrf2 as a novel regulator of desmosomes in the epidermis through the regulation of microRNAs. On Nrf2 activation, expression of miR-29a and miR-29b increases in cultured human keratinocytes and in mouse epidermis. Chromatin immunoprecipitation identified the Mir29ab1 and Mir29b2c genes as direct Nrf2 targets in keratinocytes. While binding of Nrf2 to the Mir29ab1 gene activates expression of miR-29a and -b, the Mir29b2c gene is silenced by DNA methylation. We identified desmocollin-2 (Dsc2) as a major target of Nrf2-induced miR-29s. This is functionally important, since Nrf2 activation in keratinocytes of transgenic mice causes structural alterations of epidermal desmosomes. Furthermore, the overexpression of miR-29a/b or knockdown of Dsc2 impairs the formation of hyper-adhesive desmosomes in keratinocytes, whereas Dsc2 overexpression has the opposite effect. These results demonstrate that a novel Nrf2-miR-29-Dsc2 axis controls desmosome function and cutaneous homeostasis.

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Section: Discussionmentioning

confidence: 99%

“…Rather, it also controls expression of genes with other functions, such as regulation of cell proliferation and survival 13 . Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) revealed that Nrf2 binds to promoters of genes encoding microRNAs (miRNAs, miRs) [13][14][15] , although the functional consequences remain largely unknown.…”

mentioning

confidence: 99%

A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes

et al. 2014

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“…miR-125b, which is directly regulated by Nrf2, has a controversial role in AD because it is upregulated in the brain of human AD patients and downregulated in APPswe/PSDE9 ADmouse models and in murine primary hippocampal neurons treated with soluble Ab peptide [124,125]. The authors suggest the neuroprotective role of this miR, at least in mice, reporting that miR-125b decreases the expression of the pro-apoptotic proteins Bak1 and p53, which are upregulated in some AD patients and in mouse primary cortical neurons.…”

Section: Cellular Physiologymentioning

confidence: 99%

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

Paladino

Conte

Caggiano

et al. 2018

Cell Physiol Biochem

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A general hallmark of neurological diseases is the loss of redox homeostasis that triggers oxidative damages to biomolecules compromising neuronal function. Under physiological conditions the steady-state concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are finely regulated for proper cellular functions. Reduced surveillance of endogenous antioxidant defenses and/or increased ROS/RNS production leads to oxidative stress with consequent alteration of physiological processes. Neuronal cells are particularly susceptible to ROS/RNS due to their biochemical composition. Overwhelming evidences indicate that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-linked pathways are involved in protective mechanisms against oxidative stress by regulating antioxidant and phase II detoxifying genes. As such, Nrf2 deregulation has been linked to both aging and pathogenesis of many human chronic diseases, including neurodegenerative ones such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis. Nrf2 activity is tightly regulated by a fine balance between positive and negative modulators. A better understanding of the regulatory mechanisms underlying Nrf2 activity could help to develop novel therapeutic interventions to prevent, slow down or possibly reverse various pathological states. To this end, microRNAs (miRs) are attractive candidates because they are linked to intracellular redox status being regulated and, post-transcriptionally, regulating key components of ROS/RNS pathways, including Nrf2.

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“…There appears to be a role for both miR-29 and miR-125 family members in both HSC development and leukaemic stem cell maintenance [41]. Both miR-29 and miR-125 family members have been shown to be regulated by Nrf2 [39,42]. Indeed miR-125b may be a useful marker of AML disease progression in both adult and childhood AML patients [43,44] and probably stems from its role in the development of blood cells from HSCs [45].…”

Section: Nrf2mentioning

confidence: 99%

Understanding life and death decisions in human leukaemias

MacEwan

Barrera

Keadsanti

et al. 2014

Biochemical Society Transactions

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Human leukaemia cells have an often unique ability to either undergo apoptotic cell death mechanisms or, at other times, undergo proliferative expansion, sometimes to the same stimulus such as the pluripotent cytokine TNFα (tumour necrosis factor α). This potential for life/death switching helps us to understand the molecular signalling machinery that underlies these cellular processes. Furthermore, looking at the involvement of these switching signalling pathways that may be aberrant in leukaemia informs us of their importance in cancer tumorigenesis and how they may be targeted pharmacologically to treat various types of human leukaemias. Furthermore, these important pathways may play a crucial role in acquired chemotherapy resistance and should be studied further to overcome in the clinic many drug-resistant forms of blood cancers. In the present article, we uncover the relationship that exists in human leukaemia life/death switching between the anti-apoptotic pro-inflammatory transcription factor NF-κB (nuclear factor κB) and the cytoprotective antioxidant-responsive transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2). We also discuss recent findings that reveal a major role for Btk (Bruton's tyrosine kinase) in both lymphocytic and myeloid forms of human leukaemias and lymphomas.

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miR-125b transcriptionally increased by Nrf2 inhibits AhR repressor, which protects kidney from cisplatin-induced injury

Cited by 86 publications

References 59 publications

A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes

A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

Understanding life and death decisions in human leukaemias

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