RESUMO
Metastasis-associated protein 2 (MTA2) is frequently amplified in many types of cancers; however, the role and underlying molecular mechanism of MTA2 in esophageal squamous cell carcinoma (ESCC) remain unknown. Here, we reported that MTA2 is highly expressed in ESCC tissue and cells, and is closely related to the malignant characteristics and poor prognosis of patients with ESCC. Through in vitro and in vivo experiments, we demonstrated that MTA2 significantly promoted ESCC growth, metastasis, and epithelial-mesenchymal transition (EMT) progression. This integrative analysis combined with expression microarray showed that MTA2 could interact with eukaryotic initiation factor 4E (EIF4E), which positively regulates the expression of Twist, known as a master regulator of EMT. Moreover, the results of chromatin immunoprecipitation revealed that MTA2 was recruited to the E-cadherin promoter by Twist, which reduced the acetylation level of the promoter region and thus inhibited expression of E-cadherin, and subsequently promoted the aggressive progression of ESCC. Collectively, our study provided novel evidence that MTA2 plays an aggressive role in ESCC metastasis by a novel EIF4E-Twist positive feedback loop, which may provide a potential therapeutic target for the management of ESCC.
Assuntos
Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Fator de Iniciação 4E em Eucariotos/metabolismo , Histona Desacetilases/metabolismo , Proteínas Nucleares/genética , Proteínas Repressoras/metabolismo , Proteína 1 Relacionada a Twist/genética , Animais , Antígenos CD/genética , Caderinas/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/secundário , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia , Esôfago/patologia , Esôfago/cirurgia , Fator de Iniciação 4E em Eucariotos/genética , Retroalimentação Fisiológica , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Histona Desacetilases/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Prognóstico , Regiões Promotoras Genéticas , Proteínas Repressoras/genética , Proteína 1 Relacionada a Twist/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND/AIMS: Periplocin is extracted from the traditional herbal medicine cortex periplocae, which has been reported to suppress the growth of cancer cells. However, little is known about its effect on gastric cancer cells. METHODS: Gastric cancer cells were treated with periplocin, and cell viability was assessed using MTS assay. Flow cytometry and TUNEL staining were performed to evaluate apoptosis, and protein expression was examined by western blotting. Microarray analysis was used to screen for changes in related genes. RESULTS: We found that periplocin had an inhibitory effect on gastric cancer cell viability in a dose-dependent manner. Periplocin inhibited cell viability via the ERK1/2-EGR1 pathway to induce apoptosis. Periplocin also inhibited the growth of tumor xenografts and induced apoptosis in vivo. CONCLUSION: Our results show that periplocin inhibits the proliferation of gastric cancer cells and induces apoptosis in vitro and in vivo, indicating its potential to be used as an antitumor drug.
Assuntos
Apocynaceae/química , Apoptose/efeitos dos fármacos , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Apocynaceae/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Extratos Vegetais/química , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Transplante HeterólogoRESUMO
We aimed to confirm the role of miR-1296-5p in gastric cancer and to identify its target genes. The expression of miR-1296-5p was measured in gastric cancer tissues and cell lines. The function of miR-1296-5p was examined by the overexpression and inhibition of its expression in typical gastric cell lines as well as SGC-7901 and MGC-803 cells. The targets of miR-1296-5p were identified by a luciferase activity assay. We found that miR-1296-5p was down-regulated in gastric cancer tissue and cell lines, and low expression levels of miR-1296-5p were associated with advanced clinical stage. Moreover, miR-1296-5p inhibited cell proliferation, migration, and invasion in SGC-7901 and MGC-803 cells. Then, we identified CDK6 and EGFR as novel targets of miR-1296-5p by a luciferase activity assay. Furthermore, the overexpression of miR-1296-5p suppressed the expression of CDK6 and EGFR. Our results indicated a tumor-suppressive role of miR-1296-5p through the translational repression of oncogenic CDK6 and EGFR in gastric cancer.
Assuntos
Quinase 6 Dependente de Ciclina/genética , Genes Supressores de Tumor/fisiologia , MicroRNAs/genética , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Receptores ErbB/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The aim of this study was to compare the efficacy between SBRT and surgery based on the Propensity-Matched Analysis. METHODS: Publications on comparison SBRT and Surgery for early stage non- small cell lung cancer (NSCLC) from 2011 to 2017 were collected. Propensity score matching was used to achieve comparable treatment hazard ratios of the overall survival (OS), local control survival (LC), regional control survival (RC), loco-regional control survival (LRC), distant control survival (DC), disease-free survival (DFS), and progression-free survival (PFS) between SBRT and Surgery. The major outcomes measures were hazard ratios (HRs). Meta-analysis Revman 5.3 software was used to analyze the combined Pooled HRs using fixed- or random-effects models according to the heterogeneity. RESULT: Eleven studies met our inclusion criteria. The LC, L-R C, DC, DFS and PFS rates of patients with early-stage lung cancer who were treated with SBRT are equal to surgical results. While, patients with surgery achieved superior OS compared with SBRT. CONCLUSION: In this study we carried out a meta-analysis, which controls the acceptable level of the efficacy in the propensity score to match patients. The surgery had obvious OS advantages in this meta-analysis. However, these conclusions would be proven by further studies incorporating comorbidity data, and outcomes from randomized control study. The final decision for the optimal treatment of a patient with early-stage NSCLC can be substantiated by a personalized treatment model.