RESUMEN
BACKGROUND/AIMS: Zinc Finger Protein 281 (ZNF281) was recently identified as a novel oncogene in several human carcinomas. However, the clinical significance of ZNF281 in colorectal cancer (CRC) and the molecular mechanisms by which ZNF281 promotes the growth and metastasis of CRC remain unknown. METHODS: ZNF281 expression in CRC tissues was assessed, and the outcomes were analyzed to determine the clinical importance of ZNF281 expression. Cell Transwell assays and a wound healing assay were performed to assess the effects of ZNF281 on CRC cell migration and invasion in vitro. Western blotting was applied to analyze the potential mechanisms. RESULTS: ZNF281 mRNA and protein levels were significantly increased in CRC tissues compared with normal colon tissues, and high ZNF281 expression was associated with advanced T stage, N stage, TNM stage and differentiation. Therefore, ZNF281 expression might be an independent prognostic indicator in CRC patients. Moreover, knockdown of ZNF281 expression suppressed cell proliferation, migration and invasion by inhibiting the Wnt/ß-catenin pathway. CONCLUSION: Our study indicates that ZNF281 plays a critical role in the progression and metastasis of CRC and could represent a potential therapeutic target for CRC.
Asunto(s)
Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Transactivadores/metabolismo , Anciano , Línea Celular Tumoral , Movimiento Celular/genética , Movimiento Celular/fisiología , Proliferación Celular/genética , Proliferación Celular/fisiología , Neoplasias Colorrectales/genética , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Células HT29 , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Invasividad Neoplásica/fisiopatología , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , ARN Interferente Pequeño/genética , Proteínas Represoras , Transactivadores/antagonistas & inhibidores , Transactivadores/genética , Regulación hacia Arriba , Vía de Señalización Wnt , beta Catenina/metabolismoRESUMEN
Increasing evidences indicate that dys-regulation of MicroRNAs contributes to hepatocellular carcinoma. However, the roles of miR-485-5p in HCC are still largely unexplored. In the present study, our quantitative real-time PCR analysis found that miR-485-5p was significantly down-regulated in 50 pairs of human HCC tissues. Moreover, the reduced expression of miR-485-5p was significantly correlated with larger tumor size and more tumor number in patients with HCC. In vitro studies further showed that overexpression of miR-485-5p mimics could inhibit, while its antisense oligos promote cell proliferation and invasion. Results from the dual-luciferase reporter gene assays and western blot further showed that stanniocalcin 2 was a direct target of miR-485-5p. Therefore, our data suggest a novel role for miR-485-5p in the regulation of HCC progression.
Asunto(s)
Carcinoma Hepatocelular/patología , Regulación Neoplásica de la Expresión Génica , Glicoproteínas/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Neoplasias Hepáticas/patología , MicroARNs/genética , Carcinogénesis , Carcinoma Hepatocelular/cirugía , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , Regulación hacia Abajo , Femenino , Genes Reporteros , Glicoproteínas/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neoplasias Hepáticas/cirugía , Masculino , MicroARNs/metabolismo , Persona de Mediana EdadRESUMEN
The present study aimed to construct a novel recombinant adenovirus expression vector Ad-BMP2-IRES-HIF1αmu that expresses human bone morphogenetic protein (BMP2) and mutant hypoxia-inducible factor 1α, and investigated its effects in promoting neogenesis of bone and angiogenesis. The recombinant adenovirus BMP2, HIF1αmu and pIRES2-EGFP expression vectors were constructed and transfected into HEK293A cells. The groups were divided into group A, transfection with Ad-BMP2-IRES-HIF1αmu; group B, transfection with Ad-HIF1αmu-IRES-hrGFP-1; group C, transfection with Ad-BMP2-IRES-hrGFP-1; group D, transfection with Ad-IRES-hrGFP-1; group E, not transfected. Adenovirus liquid was transferred into rabbit mesenchymal stem cells (MSCs) pretreated with dexamethasone at the best multiplicity of infection (MOI). The mRNA and protein expression of BMP2 and HIF1α were detected by RT-PCR and western blot analysis. Adenovirus was successfully packaged. The expression level of HIF1α mRNA in group A and B was markedly higher than that in groups C, D and E, showing a significant difference (P<0.01). There was a significant difference in the expression level of BMP2 mRNA between group A and C (P<0.05) and this was markedly higher than that in groups B, D and E (P<0.01). The protein expression level of HIF1α in group A and B was markedly higher than that in groups C, D and E (P<0.01). The protein expression level of BMP2 in group A and C was markedly higher than that in groups B, D and E (P<0.01). The human BMP2-IRES-HIF1αmu adenovirus expression vector was successfully constructed and the experimental groups formed bone and blood vessels prior to the positive and negative control groups.