RESUMEN
BACKGROUND: Breast cancer is one of the leading causes of death in women worldwide. Fast growth is the important character of breast cancer, which makes sure the subsequent metastasize and invasion breast cancer. Golgi related genes GOLPH3 has been reported to regulate many kinds of cancers proliferation. However, its upregulator remains largely unknown. miRNA modulate gene expression by post-transcriptional repression to participate in many signaling pathway of breast cancer cell proliferation. miR-590 has been reported to regulate tumorgenesis and could be regulated by its own target ATF-3. But whether miR-590 can be the modulator of Golgi related genes to regulate the breast cancer proliferation is unclear. METHODS: We performed the bioinformatics analysis of survival rate and expression differences of patients using the data of The Cancer Genome Atlas (TCGA).Both of MTS and BrdU assays were used for cell proliferation analysis. Cell cycle was detected by flow cytometry .qRT-PCR was used for detecting the cell cycle related gene expression. Student's t-test or One way anova was used for statistics. RESULTS: We found the upregulation of GOLPH3 in breast cancer samples compared with normal breast tissues, which also was related to the poor prognosis. Overexpression of GOLPH3 significantly promoted proliferation both of MDA-MB-231 cells (ER negative) and MCF-7 cells (ER positive). We further found that miRNA-590-3p could directly target the 3'-UTR of GOLPH3 mRNA to repress its expression. Overexpression of miR-590-3p inhibited the proliferation of MDA-MB-231 and MCF-7 cells. The rescue experiments indicated that overexpression of GOLPH3 significantly resorted the proliferation inhibited by miR-590-3p. We also found that ATF-3 repressed miR-590-3p expression to modulate miR-590/GOLPH3 pathway to regulate breast cancer cells proliferation. CONCLUSIONS: This study not only suggests that the ATF-3/miR-590/GOLPH3 signaling pathway is critically involved in the proliferation of breast cancer cells, but provides a novel therapeutic target and new insight base on epigenetic regulation for future breast cancer diagnosis and clinical treatment.
Asunto(s)
Factor de Transcripción Activador 3/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/metabolismo , MicroARNs/genética , Regiones no Traducidas 3' , Factor de Transcripción Activador 3/genética , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Ciclo Celular , Movimiento Celular , Epigénesis Genética , Femenino , Humanos , Proteínas de la Membrana/genética , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
Colorectal cancer (CRC) currently leads to many deaths worldwide. The regulatory mechanism, however, remains largely unclear. In the present study, bioinformatics methods were used to identify genes associated with CRC prognosis and to detect the molecular signals regulating the cell cycle in two CRC cell lines. It was revealed that BNIPL2 expression was higher in CRC tissues than in adjacent tissue samples. Upregulation of BNIPL2 was correlated with poor prognosis and the adverse malignant stages T and M. BNIPL2 was also associated with signaling pathways involved in cancer cell growth. BNIPL2 overexpression promoted cell proliferation and increased the proportion of cells in the G2/M phase. Knockdown of BNIPL2 inhibited cell proliferation. CD44 was regulated by BNIPL2 and promoted cell proliferation. Downregulation of CD44 suppressed cell proliferation and rescued the cell proliferation promoted by BNIPL2. Overexpression of CD44 restored the cell proliferation suppressed by BNIPL2 knockdown. The present study not only suggested that BNIPL2 may be a potential biomarker of CRC but also indicated that BNIPL2 regulates CRC cancer proliferation via CD44, which could be a diagnostic and clinical treatment target.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Receptores de Hialuranos/metabolismo , Apoptosis , Biomarcadores de Tumor , Ciclo Celular , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Perfilación de la Expresión Génica , Humanos , Estadificación de Neoplasias , Pronóstico , Transducción de SeñalRESUMEN
Rapid proliferation is one of the critical characteristics of breast cancer. However, the underlying regulatory mechanism of breast cancer cell proliferation is largely unclear. The present study indicated that sevoflurane, one of inhalational anesthetics, could significantly suppress breast cancer cell proliferation by arresting cell cycle at G1 phase. Notably, the rescue experiment indicated that miR-203 was upregulated by sevoflurane and mediated the function of sevoflurane on suppressing the breast cancer cell proliferation. The present study indicated the function of the sevoflurane/miR-203 signaling pathway on regulating breast cancer cell proliferation. These results provide mechanistic insight into how the sevoflurane/miR-203 signaling pathway supresses proliferation of breast cancer cells, suggesting the sevoflurane/miR-203 pathway may be a potential target in the treatment of breast cancer.