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- W316213751 abstract "Exposure of humans to inorganic arsenic can cause skin cancer. The acquisition of cancer stem cell-like properties is involved in the initiation of some cancers, and there are changes in let-7 levels in some tumors. The mechanisms of action, however, remain obscure. Here, we report that there are decreased levels of let-7a, let-7b, and let-7c in human keratinocyte HaCaT cells during malignant transformation induced by a low concentration (1.0 μM) of arsenite. The process by which arsenite reduces the level of let-7c apparently involves methylation, for 5-aza-2′-deoxycytidine, an inhibitor of methyltransferases, prevents arsenite-induced hypermethylation, decreases the level of let-7c, and thereby blocks arsenite-induced activation of the Ras/NF-κB signal pathway. Let-7c is an up-stream regulator of the Ras/NF-κB signal pathway and down-regulates activation of this pathway. In arsenite-transformed HaCaT cells, the acquisition of cancer stem cell-like properties is prevented by over-expression of let-7c, and over-expression of let-7c decreases the malignancy of transformed HaCaT cells. Thus, we conclude that epigenetic silencing of let-7c via Ras/NF-κB is involved in the acquisition of cancer stem cell-like properties and neoplastic transformation of HaCaT cells induced by arsenite, which contribute to the tumorigenesis of arsenite." @default.
- W316213751 created "2016-06-24" @default.
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- W316213751 date "1994-01-01" @default.
- W316213751 modified "2023-09-24" @default.
- W316213751 title "Empowering and healing the battered woman" @default.
- W316213751 doi "https://doi.org/10.1016/0272-7358(94)90009-4" @default.
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