RESUMEN
The dependence of expression of miRNAs and their precursors (pre-miRNAs) on the DNA methylation level in HeLa cells 8 days after mitomycin C treatment was studied. A massive parallel DNA sequencing method was applied to analyze miRNA expression. 5-Azacytidine (DNA methylation inhibitor) was added to the medium 6 days after mutagenic agent exposure. The results indicated that the change in expression for some mature miRNAs (39 of 61) was accompanied by the change in the expression of their pre-miRNAs, while there were no significant changes in the expression of pre-miRNA for other mature miRNAs (22 of 61). The aberrant expression was maintained by 8 of 61 mature miRNAs and 6 of 55 pre-miRNAs in the induced HeLa cells after 5-azacytidine treatment. In addition, the expression of more than 90% of miRNAs, which indicated a significant change in expression after mitomycin C treatment, does not depend or depends slightly on the DNA methylation level in HeLa cells without mitomycin C treatment. The results suggest that mitomycin C induces aberrant DNA methylation which affects maintenance of changes in the miRNA expression in cell generations after mutagen treatment.
Asunto(s)
Metilación de ADN , Regulación de la Expresión Génica/efectos de los fármacos , MicroARNs , Mitomicina/farmacología , Metilación de ADN/efectos de los fármacos , Metilación de ADN/genética , Células HeLa , Humanos , MicroARNs/biosíntesis , MicroARNs/genéticaRESUMEN
It was first shown that DNA damage induction in mitomycin C-treated HeLa cells leads to a change in the selection of 5p and 3p microRNA duplex strands in the formation of the RNA-induced silencing complex (RISC).
Asunto(s)
Daño del ADN/genética , Daño del ADN/fisiología , MicroARNs/genética , MicroARNs/metabolismo , Daño del ADN/efectos de los fármacos , Células HeLa , Humanos , Mitomicina/toxicidad , Inhibidores de la Síntesis del Ácido Nucleico/toxicidad , Complejo Silenciador Inducido por ARN/efectos de los fármacos , Complejo Silenciador Inducido por ARN/genética , Complejo Silenciador Inducido por ARN/metabolismoRESUMEN
This work is devoted to the study and obtaining of new radioprotective agents based on natural flavonoid genistein and spherical amorphous nanoparticles (SANPs) produced from a mixture of birch bark triterpenoids. The physicochemical characteristics of the nanoparticles were studied by electron microscopy, dynamic light scattering, and UV-VIS spectroscopy. The radioprotective efficacy of the nanodrug in vivo and the possibility of its use as a radioprotective agent was shown.