MicroRNAs and reactive oxygen species: Are they in the same regulatory circuit?

Jaksik, Roman; Lalik, Anna; Skonieczna, Magdalena; Cieślar-Pobuda, Artur; Student, Sebastian; Rzeszowska-Wolny, Joanna

doi:10.1016/j.mrgentox.2013.09.003

Cited by 21 publications

(16 citation statements)

References 54 publications

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“…Hyperoxia in the newborn leads to a systematic increase in ROS (Kwak et al, 2006). We postulate that these ROS can downregulate miR-96 as occurs with other miRNAs under oxidative stress conditions (Magenta et al, 2013;Jaksik et al, 2014). For instance, miR-96 in human retinal pigment epithelial cell stimulated with hydrogen peroxide (ROS inducer), was found to be strongly downregulated (Ayaz and Dinc, 2018).…”

Section: Discussionmentioning

confidence: 92%

“…Several miRNAs are modulated by reactive oxygen species (ROS) (He and Jiang, 2016;Banerjee et al, 2017), as reported in inflammation (Sonkoly and Pivarcsi, 2009), cardiovascular conditions including stroke, and in post-occlusion revascularization (Magenta et al, 2013;Jaksik et al, 2014;Gong et al, 2018). Hyperoxia in the newborn leads to a systematic increase in ROS (Kwak et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA-96 Promotes Vascular Repair in Oxygen-Induced Retinopathy—A Novel Uncovered Vasoprotective Function

et al. 2020

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Background and Aims: Vascular degeneration is a hallmark in the pathogenesis of oxygen-induced retinopathy (OIR). Dysregulation of microRNAs (miRNAs), key regulators of genes expressions, has been implicated in the regulation of ocular angiogenesis. However, miRNAs specific functions in impaired vascular development during OIR are poorly understood. Herein, we identified miR-96 as one of the most highly expressed miRNAs in the retina and choroid during vascular development and investigated the potential role of miR-96 on microvascular degeneration in a rat OIR model. Methods and Results: Next generation sequencing (NGS) and qRT-PCR analysis showed that miR-96 maintain high levels of expression during ocular vascular development. Nevertheless, miR-96 was significantly downregulated in the retina and choroid of OIR rats (80% O 2 from P5 to P10) during the phase of microvascular degeneration. Similarly, human retinal microvascular endothelial cells (HRMEC) subjected to hyperoxia (80% O 2) showed a significant downregulation of miR-96 evaluated by qPCR. Interestingly, HRMEC supplemented with miR-96 regulated positively the expression of several key angiogenic factors including VEGF and ANG-2. To explore the angiogenic activity of miR-96 on HRMEC, we performed a gain/loss of function study. In a similar way to hyperoxia exposure, we observed a robust angiogenic impairment (tubulogenesis and migration) on HRMEC transfected with an antagomiR-96. Conversely, overexpression of miR-96 stimulated the angiogenic activity of HRMEC and protected against hyperoxia-induced endothelial dysfunction. Finally, we evaluated the potential vasoprotective function of miR-96 in OIR animals. Rat pups intravitreally supplemented with miR-96 mimic (1 mg/kg) displayed a significant preservation of retinal/choroidal microvessels at P10 compared to controls. This result was consistent with the maintenance of physiologic levels of VEGF and ANG-2 in the OIR retina. Conclusion: This study demonstrates that miR-96 regulates the expression of angiogenic factors (VEGF/ANG-2) associated to the maintenance of retinal and choroidal microvasculature during physiological and pathological conditions. Intravitreal

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

MicroRNA-96 Promotes Vascular Repair in Oxygen-Induced Retinopathy—A Novel Uncovered Vasoprotective Function

et al. 2020

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“…To get more information on these mechanisms, we compared the expression of different genes coding for proteins engaged directly or indirectly in redox processes in each cell line. The expression levels of more than 500 candidate genes found on the basis of ontology terms were compared using our earlier microarray data for Me45 and HCT116 cells (17). The full list of these genes and their expression levels are given in Table S1 of the Supplement.…”

Section: Resultsmentioning

confidence: 99%

“…We identified 574 genes which are directly or indirectly engaged in redox processes, using GO terms such as oxide, superoxide, nitric oxide, hydrogen peroxide, ROS and reactive oxygen species. The levels of transcripts of these genes in non-irradiated HCT116 and Me45 cells were extracted from our earlier Affymetrix microarray experiments (32, 17) whose results are available in the ArrayExpress database under accession number E-MEXP-2623. All data are MIAME compliant.…”

Section: Methodsmentioning

confidence: 99%

Cell type-specific differences in redox regulation and proliferation after low UVA doses

Ciesielska

Bil

Gajda

et al. 2018

Preprint

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21Ultraviolet A (UVA) radiation is harmful for living organisms but in low doses may 22 stimulate cell proliferation. Our aim was to examine the relationships between exposure 23 to different low UVA doses, cellular proliferation, and changes in cellular reactive 24 oxygen species levels. In human colon cancer (HCT116) and melanoma (Me45) cells 25 exposed to UVA doses comparable to environmental, the highest doses (30-50 kJ/m 2 ) 26 reduced clonogenic potential but some lower doses (1 and 10 kJ/m 2 ) induced 27 proliferation. This effect was cell type and dose specific. In both cell lines the levels of 28 reactive oxygen species and nitric oxide fluctuated with dynamics which were 29 influenced differently by UVA; in Me45 cells decreased proliferation accompanied the 30 changes in the dynamics of H 2 O 2 while in HCT116 cells those of superoxide. Genes 31 coding for proteins engaged in redox systems were expressed differently in each cell 32 line; transcripts for thioredoxin, peroxiredoxin and glutathione peroxidase showed 33 higher expression in HCT116 cells whereas those for glutathione transferases and 34 copper chaperone were more abundant in Me45 cells. We conclude that these two cell 35 types utilize different pathways for regulating their redox status. Many mechanisms 36 engaged in maintaining cellular redox balance have been described. Here we show that 37 the different cellular responses to a stimulus such as a specific dose of UVA may be 38 consequences of the use of different redox control pathways. Assays of superoxide and 39 hydrogen peroxide level changes after exposure to UVA may clarify mechanisms of 40 cellular redox regulation and help in understanding responses to stressing factors. 41 42 43 44 Ciesielska 3 45 46 48with a wavelength of 100-400 nm, invisible to human sight. The sun is a natural emitter 49 of UV divided into three main fractions UVA (315-400 nm), UVB (280-315 nm), and 50 UVC (100-280 nm), but most of this radiation is blocked by the atmosphere (1,2). UVA 51 constitutes the largest part (∼95%) of UV radiation that reaches the Earth's surface (3), 52whereas UVB represents only 4-5% (1). In irradiated humans UVA reaches the dermis 53 and hypodermis and has no direct impact on DNA, but it can influence cellular 54 structures indirectly by induction of reactive oxygen species (ROS) which can damage 55 macromolecules (4,1). For a long time UV was regarded as damaging for cells and 56 organisms (5), but since a few decades it is known that low doses can also stimulate 57 proliferation of cells; however, the mechanisms underlying this phenomenon are not 58 completely understood (3,1,6,7). 59Studies of signaling pathways in conditions where UVA stimulates cell proliferation 60 show changes in the levels of proteins engaged in controlling proliferation such as 61 cyclin D1 (8,9), Pin1 (3), and Kin17 (10) or activation of epidermal growth factor 62 receptor (EGFR) which is strongly mitogenic in many cell types (8). Experiments on 63 mice showed that UVA can accelerate tumor growth ...

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“…The prevailing up-regulation of miRNAs after exposure to ionizing radiation has been reported in irradiated mouse testis by Tamminga et al (69), in thymus of the progeny of irradiated male mice (19, 70) and in human peripheral blood cells (71). Jaksik et al (72) reported up-regulation of miRNAs in human K562, Me45, and HCT116 cells at 1 h but not at 12 h after irradiation, whereas, e.g., Kraemer et al (70) found that the majority of deregulated miRNAs were down-regulated at 4 and 24 h after irradiation. As expected, changes in miRNA expression seem to vary as a function of time and depend on the type and dose of radiation, and target organism.…”

Section: Discussionmentioning

confidence: 99%

Role of microRNAs and DNA Methyltransferases in Transmitting Induced Genomic Instability between Cell Generations

Huumonen

Korkalainen

Viluksela

et al. 2014

Front. Public Health

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There is limited understanding of how radiation or chemicals induce genomic instability, and how the instability is epigenetically transmitted to the progeny of exposed cells or organisms. Here, we measured the expression of microRNAs (miRNAs) and DNA methyltransferases (DNMTs) in murine embryonal fibroblasts exposed to ionizing radiation or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which were previously shown to induce genomic instability in this cell line. Cadmium was used as a reference agent that does not induce genomic instability in our experimental model. Measurements at 8 and 15 days after exposure did not identify any such persistent changes that could be considered as signals transmitting genomic instability to the progeny of exposed cells. However, measurements at 2 days after exposure revealed findings that may reflect initial stages of genomic instability. Changes that were common to TCDD and two doses of radiation (but not to cadmium) included five candidate signature miRNAs and general up-regulation of miRNA expression. Expression of DNMT3a, DNMT3b, and DNMT2 was suppressed by cadmium but not by TCDD or radiation, consistently with the hypothesis that sufficient expression of DNMTs is necessary in the initial phase of induced genomic instability.

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MicroRNAs and reactive oxygen species: Are they in the same regulatory circuit?

Cited by 21 publications

References 54 publications

MicroRNA-96 Promotes Vascular Repair in Oxygen-Induced Retinopathy—A Novel Uncovered Vasoprotective Function

MicroRNA-96 Promotes Vascular Repair in Oxygen-Induced Retinopathy—A Novel Uncovered Vasoprotective Function

Cell type-specific differences in redox regulation and proliferation after low UVA doses

Role of microRNAs and DNA Methyltransferases in Transmitting Induced Genomic Instability between Cell Generations

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