The miRNA aberrant expression dependence on DNA methylation in HeLa cells treated with mitomycin C
- 37 Downloads
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.
KeywordsmiRNA DNA methylation mutagen DNA damage response mitomycin C gamma radiation
Unable to display preview. Download preview PDF.
- 15.Kraemer, A., Chen, I.P., Henning, S., et al., UVA and UVB irradiation differentially regulate microRNA expression in human primary keratinocytes, PLoS One, 2013, vol. 8, no. 12.Google Scholar
- 16.Li, Z., Branham, W.S., Dial, S.L., et al., Genomic analysis of microRNA time-course expression in liver of mice treated with genotoxic carcinogen N-ethyl-Nnitrosourea, BMC Genomics, 2010, vol. 11, no. 609.Google Scholar
- 19.Huumonen, K., Korkalainen, M., Viluksela, M., et al., Role of microRNAs and DNA methyltransferases in transmitting induced genomic instability between cell generations, Front. Public Health, 2014, vol. 2, no. 139.Google Scholar
- 21.Maniatis, T., Fritsch, E.F., and Sambrook, J., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor: Cold Spring Harbor Lab., 1982.Google Scholar
- 23.Robinson, M.D. and Smyth, G.K., Small sample estimation of negative binomial dispersion, with applications to SAGE data, Biostatistics, 2008, vol. 9, pp. 321–332.Google Scholar
- 26.Benjamini, Y. and Hochberg, Y., Controlling the false discovery rate: a practical and powerful approach to multiple testing, J. R. Stat. Soc., Ser. B Methodol., 1995, vol. 57, no. 1, pp. 289–300.Google Scholar
- 31.Li, H., Yu, G., Shi, R., et al., Cisplatin-induced epigenetic activation of miR-34a sensitizes bladder cancer cells to chemotherapy, Mol. Cancer, 2014, vol. 13, no. 8.Google Scholar
- 41.Bae, J.H., Kim, J.G., Heo, K., et al., Identification of radiation-induced aberrant hypomethylation in colon cancer, BMC Genomics, 2015, vol. 16, no. 1.Google Scholar