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1.
EMBO Rep ; 24(1): e54944, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36341538

RESUMO

Melanoma tumors are highly metastatic partly due to the ability of melanoma cells to transition between invasive and proliferative states. However, the mechanisms underlying this plasticity are still not fully understood. To identify new epigenetic regulators of melanoma plasticity, we combined data mining, tumor models, proximity proteomics, and CUT&RUN sequencing. We focus on the druggable family of bromodomain epigenetic readers and identify TRIM28 as a new regulator of melanoma plasticity. We find that TRIM28 promotes the expression of pro-invasive genes and that TRIM28 controls the balance between invasiveness and growth of melanoma cells. We demonstrate that TRIM28 acts via the transcription factor JUNB that directly regulates the expression of pro-invasive and pro-growth genes. Mechanistically, TRIM28 controls the expression of JUNB by negatively regulating its transcriptional elongation by RNA polymerase II. In conclusion, our results demonstrate that a TRIM28-JUNB axis controls the balance between invasiveness and growth in melanoma tumors and suggest that the bromodomain protein TRIM28 could be targeted to reduce tumor spread.


Assuntos
Regulação da Expressão Gênica , Melanoma , Humanos , Linhagem Celular Tumoral , Proteína 28 com Motivo Tripartido/genética , Melanoma/genética
2.
Ther Deliv ; 6(7): 855-71, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26228776

RESUMO

The natural biopolymer chitosan has versatile applications in therapeutic delivery. Coating drug delivery matrices or biomaterials with chitosan offers several advantages in drug delivery, including control of drug release, slowing degradation rate and improving biocompatibility. Advanced uses of chitosan in coating form include targeting drug delivery vehicles to specific tissue as well as providing a stimulus-controlled release response. The present review summarizes the current applications of chitosan coatings in the context of different biomaterial delivery technologies, as well as future directions of chitosan coatings for drug delivery technologies under development.


Assuntos
Quitosana/química , Portadores de Fármacos/química , Técnicas de Transferência de Genes , Animais , Química Farmacêutica , Materiais Revestidos Biocompatíveis , Preparações de Ação Retardada , Estabilidade de Medicamentos , Humanos , Cinética , Solubilidade , Tecnologia Farmacêutica/métodos
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