Single‐walled carbon nanotubes affect the expression of the CCND2 gene in human U87 glioma cells

Abstract

The effect of single-walled carbon nanotubes (SWCNTs) on the expression level of several genes, related to cell cycle control, cell proliferation and migration in human glioma cell line U87 was investigated. The exposure of human U87 glioma cells to single-walled carbon nanotubes in different concentrations during 24 of 48 h affects the expression of CCND2 (Cyclin D2), DTNA (Dystrobrevin alpha), PARVB (parvin beta), DUSP1 (dual specificity phosphatase 1), PFKFB3 (6-phosphofructo-2-kinase/ fructose-2,6-bisphosphatase-3) and PFKFB4 genes at mRNA level, as well as the expression of alternative splice variants of DTNA, PFKFB3 and PFKFB4 transcripts. In case of CCND2 gene a strong, time and dose-dependent suppressive effect was observed. The effect of single-walled carbon nanotubes on the expression level of PFKFB3, PFKFB4, and PARVB was also suppressive but less prominent. At the same time, the expression of DUSP1 and DTNA genes is up-regulated in cells treated by single-walled carbon nanotubes. Thus, single-walled carbon nanotubes exert anti-proliferative properties in U87 glioma cells, as they down-regulate the expression of proliferation-related genes (CCND2, PARVB, PFKFB3, and PFKFB4) and up-regulate DUSP1 and DTNA genes, which control apoptosis.

The impact of single walled carbon nanotubes on the expression of microRNA in zebrafish (Danio rerio) embryos

“…It has been shown that very low quantities of SWCNTs may significantly disturb the expression of microRNAs, which participate in the post-transcriptional regulation of most mRNAs and regulate variable physiological and pathophysiological processes in different cells and tissues, including brain tissue (Schratt et al 2006;Agarwal et al 2015;Matamala et al 2018;Wang et al 2018;Goldewski et al 2019;Krichevsky et al 2019;Ma et al 2019;Brennan and Henshall 2020). Previously we have shown that SWCNTs affect the expression of genes encoding enzymes and factors related to immune response, cell proliferation, and cell cycle control as well as some microRNAs in U87 glioma cells and normal human astrocytes (Minchenko et al 2016(Minchenko et al , 2018Rudnytska et al 2021). The present study indicates that SWCNTs at very low quantities significantly down-regulate the expression of numerous microRNAs in the zebrafish embryos in dose-and time-dependent manners.…”

“…It has also been shown that the above-mentioned carbon nanotubes may affect the expression of genes encoding important regulatory factors and key enzymes, which control the cell proliferation and apoptosis, such as cyclin D2, parvin beta, dystrobrevin alpha (DTNA), 6-phosphofructo-2-kinase/ fructose-2.6-bisphosphatases-3 (PFKFB3), and PFKFB4, in human U87 glioma cells (Minchenko et al 2016). It is relevant to note that SWCNTs also disturb alternative splicing of pre-mRNA, which we have demonstrated for DTNA, PFKFB3, and PFKFB4 (Minchenko et al 2016). At the same time, detailed mechanisms of this type of carbon nanotubes toxicity are still unidentified and it is possible that they may include signaling pathways of the endoplasmic reticulum stress.…”

The low doses of SWCNTs affect the expression of proliferation and apoptosis related genes in normal human astrocytes

“…Therefore, these carbon nanoparticles affect an immune response, in particular through strong suppression of the expressions of cell surface glycoproteins HLA-DRA (major histocompatibility complex, class II, DR alpha) and HLA-DRB1 and up-regulate the level of microRNAs, that possibly participate in the suppression these mRNA expression ( Minchenko et al, 2018 ). It is intertesting to note that SWCNTs also disturb alternative splicing, particularly 6-phosphofructo-2-kinase/fructose-2.6-bisphosphatase-3 (PFKFB3) and PFKFB4 as well as dystrobrevin alpha (DTNA) pre-mRNA in human U87 glioma cells ( Minchenko et al, 2016b ). Furthermore, carbon nanotubes deregulate the expression of cyclin D2, DUSP1, and lamin B1, which participate in the control of cell cycle and genome stability, as well as many other genes indicating genotoxic effect of these nanoparticles ( Minchenko et al, 2016b , 2018).…”

“…It is intertesting to note that SWCNTs also disturb alternative splicing, particularly 6-phosphofructo-2-kinase/fructose-2.6-bisphosphatase-3 (PFKFB3) and PFKFB4 as well as dystrobrevin alpha (DTNA) pre-mRNA in human U87 glioma cells ( Minchenko et al, 2016b ). Furthermore, carbon nanotubes deregulate the expression of cyclin D2, DUSP1, and lamin B1, which participate in the control of cell cycle and genome stability, as well as many other genes indicating genotoxic effect of these nanoparticles ( Minchenko et al, 2016b , 2018). However, precise mechanisms of single-walled carbon nanotubes toxicity are still largely unknown and seem to include many pathways including endoplasmic reticulum stress signaling pathways like other nanoparticles ( Barberet et al, 2017 , Cao et al, 2017 , Hu et al, 2018 , Simon et al, 2017 ).…”

Genotoxic and cytotoxic effects of titanium nitride and chromium disilicide nanoparticles as a criterion for the effect on the body

“…Раніше було показано, що фулерени C 60 і одностінні карбонові нанотрубки впливають на експресію деяких стресчутливих генів, пов'язаних з процесами проліферації клітин, їх виживання та смерті [8,9]. Виявлено зв'язок між стресом ендоплазматичного ретикулуму, який контролює численні процеси, включаючи проліферацію і виживання клітин, та різними захворюваннями, зокрема злоякіс-НАНОТЕХНОЛОГИИ И МЕДИцИНА ними пухлинами і метаболічними захворюваннями [4,5,10].…”