RESUMO
Background: The involvement of the androgen and androgen receptor (AR) pathway in the development of epithelial ovarian cancer is increasingly recognized. However, the specific mechanisms by which anti-androgen agents, such as flutamide, may prevent ovarian cancer and their efficacy remain unknown. We examined the effects of flutamide on the miRNA expression profile found in women at high risk (HR) for ovarian cancer. Methods: Ovarian and tubal tissues, free from ovarian, tubal, peritoneal cancers, and serous tubal intraepithelial carcinoma (STIC), were collected from untreated and flutamide-treated HR women. Low-risk (LR) women served as controls. Transcriptomic miRNA sequencing was performed on these 3 sample cohorts. The miRNAs that showed the most notable differential expression were subjected to functional assays in primary ovarian epithelial cells and ovarian cancer cells. Results: Flutamide treatment demonstrated a normalization effect on diminished miRNA levels in HR tissues compared to LR tissues. Particularly, the miR-449 family was significantly upregulated in HR ovarian tissues following flutamide treatment, reaching levels comparable to those in LR tissues. MiR-449a and miR-449b-5p, members of the miR-449 family, were computationally predicted to target the mRNAs of AR and colony-stimulating factor 1 receptor (CSF1R, also known as c-fms), both of which are known contributors to ovarian cancer progression, with emerging evidence also supporting their roles in ovarian cancer initiation. These findings were experimentally validated in primary ovarian epithelial cells and ovarian cancer cell lines (SKOV3 and Hey): flutamide treatment resulted in elevated levels of miR-449a and miR-449b-5p, and introducing mimics of these miRNAs reduced the mRNA and protein levels of CSF1R and AR. Furthermore, introducing miR-449a and miR-449b-5p mimics showed inhibitory effects on the migration and proliferation of ovarian cancer cells. Conclusion: Flutamide treatment restored the reduced expression of miR-449a and miR-449b-5p in HR tissues, thereby decreasing the expression of CSF1R and AR, functional biomarkers associated with an increased risk of ovarian cancer. In addition to the known direct binding of flutamide to the AR, we found that flutamide also suppresses AR expression via miR-449a and miR-449b-5p upregulation, revealing a novel dual-inhibitory mechanism on the AR pathway. Taken together, our study highlights mechanisms supporting the chemopreventive potential of flutamide in ovarian cancer, particularly in HR patients with reduced miR-449 expression.
RESUMO
Introducción: La etapa universitaria es un proceso determinante para consolidar los hábitos de vida, donde los estudiantes se ven obligados a cambiar la mayoría de sus hábitos, que propician una mala alimentación, pobre organización del tiempo y menor actividad física, teniendo repercusiones en la condición y estructura física, lo que puede afectar considerablemente el estado de salud de esta población. Objetivo: El objetivo de este trabajo fue determinar las diferencias en la composición corporal y actividad física en estudiantes universitarios según su año de ingreso. Materiales y métodos: Participaron en el estudio 287 estudiantes de ambos sexos (171 mujeres y 116 hombres), pertenecientes a las facultades de "Filosofía y Educación", "Ingenierías" y "Ciencias", a los cuales se les realizó una evaluación antropométrica para estimar la composición corporal con las ecuaciones de De Rose y Guimaraes y un cuestionario de frecuencia de actividad física. Resultados: Los resultados indican que existen diferencias en el Índice de Masa Corporal y masa grasa entre estudiantes mujeres de 1º y 2º año y entre 1º y 5º año en los hombres. La masa muscular no presenta grandes diferencias entre los grupos, pero si se aprecia cambios negativos entre el Índice de Masa Corporal y masa grasa de estudiantes que recién ingresan versus los estudiantes de último año. Conclusiones: Durante la universidad se vive un periodo crítico que afecta el nivel actividad física y el estado nutricional de los estudiantes y que podría empeorar en estudiantes con más años en la universidad.
Introduction: The university stage is a determining process when consolidating people's habits of life, where students are forced to change most of their habits favoring a poor diet, poor organization of time and less physical activity, which at the same time, has an impact on the condition and physical structure and can significantly affect the health status of this population. Objective: To determine the differences in body composition and physical activity in university students according to their year of admission. Materials and methods: The study involved 287 male and female students (171 women and 116 men) who belonged to the faculties of Philosophy and Education, Engineering and Science, who underwent an anthropometric assessment to estimate body composition with De Rose and Guimaraes equations and a frequency of physical activity questionnaire. Results: The results show that there are differences in Body Mass Index and fat mass among female students of first and second year and between the first and fifth year in men. Muscle mass had no significant differences between groups, but there is negative changes between Body Mass Index and fat mass from students newly admitted versus students in their last year. Conclusions: During the university stage, students face a critical period that affects their physical activity level and nutritional status, which could get worse for students with more years at the university.