Differential epigenetic and transcriptional profile in MCF-7 breast cancer cells exposed to cadmium.

ABSTRACT

Cadmium (Cd) has been confirmed to be associated with breast carcinogenesis, but the mechanism was not clarified yet. Given that epigenetic modification was speculated as underlying mechanism, we examined the differential epigenome caused by Cd in breast cancer cells. Profiles of DNA methylation, microRNA (miRNA), long non-coding RNA (lncRNA), and message RNA (mRNA) were derived from Cd-treated and untreated MCF-7 breast cancer cells by microarray. We identified 997 target genes epigenetically regulated by Cd through cross-verification with the differential epigenome and transcriptome, and 400 of them were further validated in a breast cancer cohort. Biological function analyses suggested that several pathways were involved in Cd-induced breast carcinogenesis, such as Wnt signaling, metabolism, and human papilloma virus (HPV) infection. TXNRD1 and CCT3 were further identified as the critical genes based on the degree of expression change, hazard ratio difference, and connectivity. The present study revealed that Cd epigenetically regulated several pathways involving in breast carcinogenesis, particularly the Wnt signaling and metabolic pathways, among which TXNRD1 and CCT3 might play critical roles. It was also suggested that Cd and HPV infection might jointly participate in breast tumorigenesis.