MicroRNAs as participants in cytotoxicity of CdTe quantum dots in NIH/3T3 cells

Abstract

Epigenetic aspects of the cytotoxicity of CdTe quantum dots (QDs) recently have attracted more attention for their ability to reprogram gene expression after initial signals have been removed. And the involvement of epigenetic mechanisms in microRNA (miRNA) biogenesis suggests that miRNAs act as participants in the cytotoxicity of CdTe QDs. According to the results of SOLiD sequencing, the expression patterns of miRNAs are widely affected after CdTe QD exposure, resulting in the apoptosis-like cell death. Compared with 86 miRNAs with down-regulated expression, the expression levels of 121 miRNAs are up-regulated by CdTe QD treatment. The Z-test is used to find out miRNAs with significantly regulated expression, and the results indicate that the expression levels of 16 and 35 miRNAs are down- and up-regulated, respectively. And the expression levels of some significantly regulated miRNAs have time- and dose-dependent tendencies, which are similar to cell survival ratios affected by CdTe QDs. The fluctuations of miRNA expression start from the transcription of pri-miRNA, and are strengthened by the processing of pri-miRNA to pre-miRNA. As a regulator in miRNA biogenesis, p53 is involved in the transcription and processing of pri-miRNA. With no significant changes in the mRNA levels of p53, the increase in overall p53 protein levels and its post-translational modification by phosphorylation at Ser-15 are induced by CdTe QD treatment. Therefore, the differential expression of miRNAs are induced by CdTe QDs at the processing of miRNA biogenesis, which is an adaptive process of cells to external stimuli.