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• W2515908727 endingPage "243" @default.
• W2515908727 startingPage "235" @default.
• W2515908727 abstract "Increasing evidence has demonstrated that in several tumors c-myc acts either as an oncogène or as a proapoptotic agent, depending on binding partner interactions. Recently, we showed that up-regulation of this gene by the histone deacetylase inhibitor MS-275 was responsible for sensitization to TRAIL-induced apoptosis through c-FLIP repression in melanoma. The present study aimed at investigating whether, in addition to inducing H3 hyperacetylation at the c-myc promoter, MS-275 could enhance cell death through the regulation of miRNAs involved in apoptosis, such as the miR-17-92 cluster. Following MS-275 treatment, a decrease in miR-92a-3p was observed either in TRAIL-resistant or TRAIL-sensitive cutaneous and uveal melanoma cells. Prediction tools revealed that miR-92a-3p targeted MYCBP2. Gain- and loss-of-function experiments showed that the 3′-UTR of MYCBP2 mRNA was the target of miR-92a-3p, as ectopic expression of miR-92a-3p resulted in MYCBP2 downregulation whereas miR-92a-3p knockdown markedly increased the expression of MYCBP2. Silencing of MYCBP2 counteracted the pro-apoptotic effects exerted by the down-regulation of miR-92a-3p and prevented c-myc-induced repression of c-FLIP, indicating a pivotal role of MYCBP2 as a mediator of miR-92a-3p and c-myc function. Together, our findings indicate that the MS-275-triggered downregulation of the oncogenic miR-92a-3p- which leads to the overexpression of its target gene MYCBP2 - is an event required for the enhanced susceptibility of melanoma cells to TRAIL-mediated apoptosis. Our data illustrate another epigenetic mechanism activated by MS-275 at the post-transcriptional level in melanoma, in addition to its best-known effects at the transcriptional level." @default.
• W2515908727 created "2016-09-16" @default.
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• W2515908727 date "2016-11-01" @default.
• W2515908727 modified "2023-10-18" @default.
• W2515908727 title "miR-92a-3p and MYCBP2 are involved in MS-275-induced and c-myc-mediated TRAIL-sensitivity in melanoma cells" @default.
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• W2515908727 doi "https://doi.org/10.1016/j.intimp.2016.09.004" @default.
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