Asunto(s)
Metilación de ADN/genética , Epigénesis Genética , Histonas/genética , Histona Demetilasas con Dominio de Jumonji/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Genoma Humano/genética , Histonas/metabolismo , Humanos , Histona Demetilasas con Dominio de Jumonji/metabolismo , Masculino , Persona de Mediana Edad , LinajeRESUMEN
AIM: Cancer stem cells (CSCs) drive triple-negative breast cancer recurrence via their properties of self-renewal, invasiveness and radio/chemotherapy resistance. This study examined how CSCs might sustain these properties. MATERIALS & METHODS: Transcriptomes, DNA methylomes and histone modifications were compared between CSCs and non CSCs. RESULTS: Transcriptome analysis revealed several pathways that were activated in CSCs, whereas cell cycle regulation pathways were inhibited. Cell development and signaling genes were differentially methylated, with histone methylation analysis suggesting distinct H3K4me2 and H3K27me3 enrichment profiles. An integrated analysis revealed several tumor suppressor genes downregulated in CSCs. CONCLUSION: Differential activation of various signaling pathways and genes contributes to the tumor-promoting properties of CSCs. Therapeutic targets identified in the analysis may contribute to improving treatment options for patients.
Asunto(s)
Neoplasias de la Mama/genética , ADN/metabolismo , Regulación Neoplásica de la Expresión Génica , Histonas/metabolismo , Células Madre Neoplásicas/metabolismo , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Epigénesis Genética , Femenino , Humanos , Metilación , TranscriptomaRESUMEN
UTX is known as a general factor that activates gene transcription during development. Here, we demonstrate an additional essential role of UTX in the DNA damage response, in which it upregulates the expression of ku80 in Drosophila, both in cultured cells and in third instar larvae. We further showed that UTX mediates the expression of ku80 by the demethylation of H3K27me3 at the ku80 promoter upon exposure to ionizing radiation (IR) in a p53-dependent manner. UTX interacts physically with p53, and both UTX and p53 are recruited to the ku80 promoter following IR exposure in an interdependent manner. In contrast, the loss of utx has little impact on the expression of ku70, mre11, hid and reaper, suggesting the specific regulation of ku80 expression by UTX. Thus, our findings further elucidate the molecular function of UTX.