In eukaryotes, genomic DNA is compacted into chromatin, with nucleosomes acting as its basic structural units. In addition to canonical nucleosomes, noncanonical nucleosomes, such as hexasomes, H3–H4 octasomes, and o...
Ultrasound (US)-mediated delivery is considered relatively safe and achieves tissue-specific targeting by simply adjusting the application site of the physical energy. Moreover, combining US with micro- or nanobubbles...
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In eukaryotic cells, genomic DNA is compacted by nucleosomes, as basic repeating units, into chromatin. The nucleosome arrangement in chromatin fibers could be an important determinant for chromatin folding, by which ...
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BACKGROUND:We investigated the role of Nuclear Receptor Binding SET Domain Protein 2 (NSD2) and microRNAs (miRNAs) in melanoma de-differentiation following Romidepsin and Interferon-α2b (RI) treatment. Melanoma is th...
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BACKGROUND:We investigated the role of Nuclear Receptor Binding SET Domain Protein 2 (NSD2) and microRNAs (miRNAs) in melanoma de-differentiation following Romidepsin and Interferon-α2b (RI) treatment. Melanoma is the most lethal form of skin cancer, and despite advancements in therapy, treatment resistance remains a major challenge. De-differentiation has been widely recognized as a key factor contributing to therapy resistance.
METHODS:RNA-seq and TCGA transcriptomic data were re-analyzed to identify miRNAs and NSD2 expressions. The functional impact of selected miRNAs was then investigated at the molecular and phenotypic levels using primary and immortalized cell lines.
RESULTS:Our findings demonstrate that RI treatment induces a de-differentiation process in primary melanoma cells, resembling that observed in therapy-resistant melanoma. This effect is particularly pronounced in cells with an intrinsic proliferative phenotype, where we observed significant downregulation of NSD2, a key epigenetic regulator implicated in multiple cancers. Additionally, we identified specific miRNAs as mediators of NSD2 downregulation, influencing melanoma cell viability and fitness.
CONCLUSIONS:These findings provide new insights into the molecular mechanisms driving melanoma progression and highlight potential therapeutic targets to counteract treatment resistance.
The nucleosome core particle (NCP) comprises a histone octamer, wrapped around by ∼146-bp DNA, while the nucleosome additionally contains linker DNA. We previously showed that, in the nucleosome, H4 N-tail acetylatio...
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The nucleosome core particle (NCP) comprises a histone octamer, wrapped around by ∼146-bp DNA, while the nucleosome additionally contains linker DNA. We previously showed that, in the nucleosome, H4 N-tail acetylation enhances H3 N-tail acetylation by altering their mutual dynamics. Here, we have evaluated the roles of linker DNA and/or linker histone on H3 N-tail dynamics and acetylation by using the NCP and the chromatosome (i.e., linker histone H1.4-bound nucleosome). In contrast to the nucleosome, H3 N-tail acetylation and dynamics are greatly suppressed in the NCP regardless of H4 N-tail acetylation because the H3 N-tail is strongly bound between two DNA gyres. In the chromatosome, the asymmetric H3 N-tail adopts two conformations: one contacts two DNA gyres, as in the NCP; and one contacts linker DNA, as in the nucleosome. However, the rate of H3 N-tail acetylation is similar in the chromatosome and nucleosome. Thus, linker DNA and linker histone both regulate H3-tail dynamics and acetylation.
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