RESUMO
Metastasis is a major cause of breast cancer mortality and the current study found histone demethylase, KDM2A, expression to be negatively correlated with breast cancer metastasis. KDM2A knockdown greatly promoted migration and invasion of breast cancer cells. The histone demethylase activity of KDM2A downregulated EGF transcription and suppressed the EGF-TSPAN8 pathway. Inhibition of breast cancer cell migration was also dependent on the histone demethylase activity of KDM2A. A novel mechanism of KDM2A-suppression of the EGF-TSPAN8 pathway which inhibited breast cancer cell migration and invasion is reported.
Assuntos
Neoplasias da Mama , Proteínas F-Box , Histona Desmetilases com o Domínio Jumonji , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proliferação de Células/fisiologia , Fator de Crescimento Epidérmico/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji/metabolismo , Tetraspaninas/metabolismoRESUMO
SETDB2 is a H3K9 histone methyltransferase required for accurate chromosome segregation. Its H3K9 histone methyltransferase activity was reported to be associated with chromosomes during metaphase. Here, we confirm that SETDB2 is required for mitosis and accurate chromosome segregation. However, these functions are independent of its histone methyltransferase activity. Further analysis showed that SETDB2 can interact with BUBR1, and is required for CDC20 binding to BUBR1 and APC/C complex and CYCLIN B1 degradation. The ability of SETDB2 to regulate the binding of CDC20 to BUBR1 or APC/C complex, and stabilization of CYCLIN B1 are also independent of its histone methyltransferase activity. These results suggest that SETDB2 interacts with BUBR1 to promote binding of CDC20 to BUBR1 and APC3, then degrades CYCLIN B1 to ensure accurate chromosome segregation and mitosis, independently of its histone methyltransferase activity.
Assuntos
Segregação de Cromossomos , Proteínas Serina-Treonina Quinases , Proteínas Serina-Treonina Quinases/metabolismo , Ciclossomo-Complexo Promotor de Anáfase/genética , Ciclossomo-Complexo Promotor de Anáfase/metabolismo , Ciclina B1/genética , Ciclina B1/metabolismo , Proteínas Cdc20/genética , Proteínas Cdc20/metabolismo , Fuso Acromático/metabolismo , Proteínas de Ciclo Celular/genéticaRESUMO
Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and is associated with high morbidity and mortality. We aimed to study the effects of microRNA-3648 (miR-3648) on LUAD by inhibiting its downstream target suppressor of cytokine signaling 2 (SOCS2) mRNA. miR-3648 expression was measured by real-time quantitative PCR in LUAD and normal lung epithelial cell lines. The direct interaction between miR-3648 and SOCS2 mRNA was identified through luciferase reporter and RNA pull-down assays. Cell viability, migration, and invasion were examined using cell functional assays. MiR-3648 was found to be overexpressed in LUAD cells and tissues. Overexpression of miR-3648 significantly enhanced cell proliferation, migration, and invasion abilities in LUAD cells. Furthermore, SOCS2 was targeted by miR-3648, and co-transfection of a miR-3648 inhibitor or si-SOCS2 reversed the suppressive effects of SOCS2 in PC9 and A549 cells. miR-3648 enhanced the proliferation and promoted migration and invasion of LUAD by inhibiting SOCS2. In conclusion, our results indicate that miR-3648 plays a pivotal role in LUADe progression and might thus provide a novel therapeutic strategy for patients with LUAD.
Assuntos
Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , MicroRNAs/fisiologia , Proteínas Supressoras da Sinalização de Citocina/genética , Células A549 , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Identifying novel differentiating agents to promote leukemia-cell differentiation is a pressing need. Here, we demonstrated that vibsanol A, a vibsane-type diterpenoid, inhibited the growth of acute myeloid leukemia (AML) cells via induction of cell differentiation, which was characterized by G1 cell cycle arrest. The differentiation-inducing effects of vibsanol A were dependent upon protein kinase C (PKC) activation, and subsequent activation of the extracellular signal-regulated kinase (ERK) pathway. Furthermore, vibsanol A treatment increased reactive oxygen species (ROS) levels, and the ROS scavenger NAC reversed the vibsanol A-induced cell differentiation, indicating an important role for ROS in the action of vibsanol A. Finally, vibsanol A exhibited a differentiation-enhancing effect when used in combination with all-trans retinoic acid in AML cells. Overall results suggested that vibsanol A induces AML cell differentiation via activation of the PKC/ERK signaling and induction of ROS. Vibsanol A may prove to be an effective differentiating agent against AML.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Diterpenos/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Linhagem Celular Tumoral , Diterpenos/isolamento & purificação , Diterpenos/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais , Sequestradores de Radicais Livres/farmacologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Leucemia Mieloide Aguda/patologia , Inibidores de Proteínas Quinases/isolamento & purificação , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Viburnum/químicaRESUMO
Saponins was applied to enhance the removal of n-hexane in a biotrickling filter (BTF) in this study. Comparison experiments were carried out to examine the effect of saponins on n-hexane removal in two BTFs at various saponins concentrations, n-hexane loading rates (LRs) and gas empty bed contact times (EBCTs). Results show that the optimum concentration of saponins in nutrient feed was 50.0mgL(-1). When organic LR of n-hexane increased from 47.8 to 120.0gm(-3)h(-1), the removal efficiency (RE) for BTF1 (with saponins) and BTF2 (without saponins) decreased from 91.3% to 83.3% and from 62.8% to 56.8%, respectively. As gas EBCT decreased from 30.0 to 7.5s, the RE declined from 88.4% to 64.5% for BTF1 and from 61.4% to 38.3% for BTF2. Saponins could also decrease the biomass accumulation rate within the medium bed. These results could be referred in the design and operation of BTFs for hydrophobic VOC removal.