RESUMO
UNLABELLED: Chemotherapy treatment is the standard in triple negative breast cancers, a cancer subgroup which lacks a specific target. The mechanisms leading to the response, as well as any markers that allow the differentiation between responder and non-responder groups prior to treatment are unknown. In parallel, miRNAs can act as oncogenes or tumor suppressors and there is evidence of their involvement in promoting resistance to anticancer drugs. Therefore we hypothesized that changes in miRNA expression after doxorubicin treatment may also be relevant in treatment response. OBJECTIVE: To study miRNAs that are differentially expressed in response to doxorubicin treatment. METHODS: One luminal-A and two triple negative, breast cancer cell lines were exposed to doxorubicin. Microarray analysis was performed to identify the common and differentially modified miRNAs. Genes and pathways that are theoretically regulated by these miRNAs were analyzed. RESULTS: Thirteen miRNAs common to all three lines were modified, in addition to 25 that were specific to triple negative cell lines, and 69 that changed only in the luminal-A cell line. This altered expression pattern seemed to be more strongly related to the breast cancer subgroup than to the treatment. The analysis of target genes revealed that cancer related pathways were the most affected by these miRNAs, moreover many of them had been previously related to chemotherapy resistance; thus suggesting follow-up studies. Additionally, through functional assays, we showed that miR-548c-3p is implicated in doxorubicin-treated MCF-7 cell viability, suggesting a role for this miRNA in resistance.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , MicroRNAs/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Células MCF-7 , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos/métodosRESUMO
Down syndrome (DS), one of the most common birth defects and the most widespread genetic cause of intellectual disabilities, is caused by extra genetic material on chromosome 21 (HSA21). The increased genomic dosage of trisomy 21 is thought to be responsible for the distinct DS phenotypes, including an increased risk of developing some types of childhood leukemia and germ cell tumors. Patients with DS, however, have a strikingly lower incidence of many other solid tumors. We hypothesized that the third copy of genes located in HSA21 may have an important role on the protective effect that DS patients show against most types of solid tumors. Focusing on Copy Number Variation (CNV) array data, we have generated frequencies of deleted regions in HSA21 in four different tumor types from which DS patients have been reported to be protected. We describe three different regions of deletion pointing to a set of candidate genes that could explain the inverse comorbidity phenomenon between DS and solid tumors. In particular we found RCAN1 gene in Wilms tumors and a miRNA cluster containing miR-99A, miR-125B2 and miR-LET7C in lung, breast, and melanoma tumors as the main candidates for explaining the inverse comorbidity observed between solid tumors and DS.
RESUMO
El objetivo fundamental del estudio consiste en identificar y evaluar las principales variables psicológicas que están interviniendo en los distintos niveles de rendimiento en la práctica de baile deportivo. Para esto, entre otros, se utilizó el Cuestionario de Características Psicológicas aplicadas al Rendimiento Deportivo (Gimeno, Buceta & Pérez-Llantada, 2001). Se realizó un análisis de varianza, y pese a no alcanzar las diferencias valores estadísticamente significativos en los factores Control del Estrés e Influencia de la Evaluación del Rendimiento, sí se puede señalar la existencia de diferencias relevantes en función de la interacción de dos condiciones: el nivel competitivo y el éxito deportivo, presentando tamaños del efecto relevantes (η²p = 0.230; η²p = 0.164). Esta información ha sido la base para realizar un posterior trabajo aplicado, ajustado a las demandas de rendimiento en este deporte.
The aim of this study is to identify and assess key psychological variables are intervening at different levels of performance in sport dance practice. For this reason, among others, was used the "Cuestionario de Características Psicológicas aplicadas al Rendimiento Deportivo" (Gimeno, Buceta & Pérez-Llantada, 2001). Carrying out an analysis of variance, although not reaching statistically significant differences in the factors Stress Management and Influence of Performance Measurement, if we can indicate the existence of relevant differences in terms of interaction two conditions: "Competitive level" and "sporting success" presenting relevant effect sizes (η²p = 0.230; η²p = 0.164). This information is a basis for applied work adjusted to the demands of performance in this sport.