5-Aza-2'-deoxycytidine advances the epithelial-mesenchymal transition of breast cancer cells by demethylating Sipa1 promoter-proximal elements.
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| Abstract |
Human breast cancer cells exhibit considerable diversity in the methylation status of genomic DNA CpGs that regulate metastatic transcriptome networks. In this study, we identified human Sipa1 promoter-proximal elements that contained a CpG island and demonstrated that the methylation status of the CpG island was inversely correlated with SIPA1 protein expression in cancer cells. 5-Aza-2'-deoxycytidine (5-Aza-CdR), a DNA methyltransferase inhibitor, promoted the expression of Sipa1 in the MCF7 breast cancer cells with a low level of SIPA1 expression. On the contrary, in MDA-MB-231 breast cancer cells with high SIPA1 expression levels, hypermethylation of the CpG island negatively regulated the transcription of Sipa1 In addition, the epithelial-mesenchymal transition (EMT) was reversed after knocking down Sipa1 in MDA-MB-231 cells. However, the EMT was promoted in MCF7 cells with over-expression of SIPA1 or treated with 5-Aza-CdR. Taken together, hypomethylation of the CpG island in Sipa1 promoter-proximal elements could enhance SIPA1 expression in breast cancer cells, which could facilitate EMT of cancer cells, possibly increasing a risk of cancer cell metastasis in individuals treated with 5-Aza-CdR.
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| Authors | Ang Lu, Wei Wang, Shu-Fang Wang-Renault, Brian Z Ring, Yoshimasa Tanaka, Jun Weng, Li Su |
| Journal | Journal of cell science (J Cell Sci) Vol. 133 Issue 9 (05 11 2020) ISSN: 1477-9137 [Electronic] England |
| PMID | 32193333 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2020. Published by The Company of Biologists Ltd. |
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