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The aim of this study was to investigate whether PRRX2 may regulate the liver metastasis of colon cancer via the Wnt/ß-catenin signaling pathway. PRRX2 and ß-catenin in patients with the liver metastases of colon cancer was detected by immunochemistry. Colon cancer cells (CT-26 and CMT93) were divided into Normal, si-Ctrl, si-PRRX2 and si-PRRX2 +LiCl groups. Cell invasive and migrating abilities and the related proteins were detected. Liver-metastatic mice model was constructed consisting of Normal, NC shRNA and PRRX2 shRNA groups to examine the function of PRRX2 shRNA on liver metastasis. We found that PRRX2 and ß-catenin positive rate was elevated in colon cancer tissues, especially in those tissues with liver metastasis, and there was a close relation between PRRX2 and the clinical staging, lymph node metastasis and numbers of liver metastases of colon cancer patients with liver metastasis. In vitro, the invasive and migrating abilities of CT-26 and CMT93 cells decreased apparently in the si-PRRX2 group, with down-regulation of PRRX2, p-GSK3ßSer9/GSK3ß, nucleus and cytoplasm ß-catenin, TCF4 and Vimentin but up-regulation of E-cadherin. However, LiCl, the Wnt/ß-catenin pathway activator, can reverse the inhibitory effect of si-PRRX2 on invasive and migrating ability of colon cancer cells. In vivo, the volume and weight of transplanted tumor and the number of liver metastases in the PRRX2 shRNA group were significantly reduced, with the similar protein expression patterns as in vitro. In a word, PRRX2 inhibition may reduce invasive and migrating abilities to hinder epithelial-mesenchymal transition (EMT), and suppress colon cancer liver metastasis through inactivation of Wnt/ß-catenin pathway.
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Neoplasias del Colon/patología , Proteínas de Homeodominio/metabolismo , Neoplasias Hepáticas/secundario , Vía de Señalización Wnt/fisiología , Anciano , Cadherinas/metabolismo , Movimiento Celular/fisiología , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Metástasis Linfática , Masculino , Persona de Mediana Edad , ARN Interferente Pequeño , Vimentina/metabolismo , beta Catenina/metabolismoRESUMEN
In this study, we aimed to explore the expression profiles of some known functional lncRNAs in esophageal adenocarcinoma (EAD) and to screening the potential prognostic makers, using data from The Cancer Genome Atlas (TCGA)-esophageal carcinoma (ESCA). Results showed that DLEU2 is a high potential OS related marker among 73 functional lncRNAs. DLEU2 and its intronic miR-15a and miR-16-1 expression were significantly upregulated in EAD compared with adjacent normal tissues. However, miR-15a and miR-16-1 expression were only weakly correlated with DLEU2 expression. Univariate and multivariate analysis confirmed that DLEU2 expression, but not miR-15a or miR-16-1 expression is an independent prognostic marker in terms of OS (HR:1.688, 95%CI: 1.085-2.627, p = 0.020) in EAD patients. The exon 9 of DLEU2 is very strongly co-expressed with DLEU2 (Pearson's r = 0.96) and showed better predictive value than total DLEU2 expression in predicting the OS of EAD patients. Multivariate analysis confirmed its independent prognostic value (HR:1.970, 95%CI: 1.266-3.067, p = 0.003), after adjustment of histologic grade, pathological stages and the presence of residual tumor. By checking the methylation status of DLEU2 gene, we excluded the possibility of the influence of two CpG sites near the DLEU2 exon 9 locus on its expression. In addition, although copy number alterations (CNAs) were observed DLEU2 gene, heterozygous loss (-1), low-level copy gain (+1) and high-level amplification (+2) had no significant association with DLEU2 transcription. Based on these findings, we infer that DLEU2 exon 9 expression might serve as a valuable biomarker of unfavorable OS in EAD patients.
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Adenocarcinoma/metabolismo , Biomarcadores de Tumor/biosíntesis , Neoplasias Esofágicas/metabolismo , Exones/genética , ARN Largo no Codificante/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Islas de CpG/genética , Epigénesis Genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidad , Femenino , Humanos , Modelos Lineales , Masculino , Pronóstico , ARN Largo no Codificante/genética , Análisis de Supervivencia , Transferasas , Proteínas Supresoras de Tumor/genética , Regulación hacia ArribaRESUMEN
AIM: To explore the relationship between serum p53 antibodies (p53-Abs) and clinicopathological characteristics and therapeutic effect in patients with esophageal carcinoma (EC), and to investigate sequential changing regularity of serum p53-Abs after radiotherapy. METHODS: The serum p53-Ab levels were detected in 46 EC patients and 30 healthy adults by enzyme linked immunosorbent assay (ELISA). The blood samples were collected on the day before radiotherapy and on the administration of an irradiation dose of 20 Gy/10 f/12 d, 40 Gy/20 f/24 d and 60 Gy/30 f/36 d after radiotherapy. RESULTS: The level and positive rate of serum p53-Abs in EC patients were significantly higher than those in normal individuals (P<0.05). Serum anti-p53 antibodies were positive in 18 of 46 EC patients (39.1%). The positive rate of p53-Abs in EC was related to histological grade, disease stage and lymph node metastasis (P<0.05), but it was not significantly related to sex, age and to the size and site of tumor. The level and positive rate of p53-Abs had significant differences between before radiotherapy and after administration of an irradiation dose of 40 Gy/20 f/24 d and 60 Gy/30 f/36 d (P<0.05 or P<0.01). The positive rate of p53-Abs in EC patients with effect was significantly lower than that in those without effect after radiotherapy (P<0.0001). CONCLUSION: Detection of serum p53-Abs is helpful to the diagnosis of esophageal carcinoma. Monitoring for sequential change of serum p53-Abs before and after radiotherapy in patients with esophageal carcinoma is also useful to evaluate the response to the treatment and prognosis of the patients.
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Autoanticuerpos/sangre , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , Proteína p53 Supresora de Tumor/inmunología , Anciano , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Relación Dosis-Respuesta en la Radiación , Ensayo de Inmunoadsorción Enzimática , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/patología , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: Microfibril-associated protein 2 (MFAP2) is an extracellular matrix protein that interacts with fibrillin to modulate the function of microfibrils. MFAP2 has been reported to play a significant role in obesity, diabetes, and osteopenia, and has been shown to be upregulated in head and neck squamous cell carcinoma. However, the molecular function and prognostic value of MFAP2 have never been reported in gastric cancer (GC) or any other tumors. METHODS: The current study investigated the expression patterns, prognostic significance, functional role, and possible mechanisms of MFAP2 in GC. RESULTS: We demonstrated that MFAP2 was overexpressed in GC tissues, and its overexpression was significantly correlated with poor overall and disease-free survival in patients with GC. Moreover, we found that MFAP2 promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) phenotype in GC cells. MFAP2 might modulate EMT of GC cells by activating the TGF-ß/SMAD2/3 signaling pathway. CONCLUSION: These findings provide novel evidence that MFAP2 plays a crucial role in the progression of GC. Therefore, MFAP2 may be a promising prognostic marker and a potent anticancer agent.
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Oleuropein is a polyphenol, that is found in extravirgin olive oil. Previous studies have shown that oleuropein inhibits cell proliferation and induces apoptosis in breast cancer, colorectal cancer and thyroid cancer. The aim of the present study was to investigate the effects of oleuropein in hepatocellular carcinoma (HCC) cells. The results of Cell Counting Kit 8 and flow cytometric analysis indicated that oleuropein effectively inhibited cell viability and induced apoptosis in HepG2 human hepatoma cells in a dosedependent manner, through activation of the caspase pathway. Proapoptotic Bcl2 family members, BAX and Bcl2, were involved in oleuropeininduced apoptosis. The phosphatidylinositol 3kinase/protein kinase B (PI3K/AKT) signaling pathway was also shown to be involved in this process. Oleuropein was demonstrated to suppress the expression of activated AKT. In addition, AKT overexpression promoted cell survival following treatment with oleuropein, while inhibition of AKT promoted cell death. Furthermore, the data demonstrated that oleuropein induces the production of reactive oxygen species (ROS) and that the function of oleuropein is, at least partially, ROSdependent. These results suggest that oleuropein may be a promising novel chemotherapeutic agent in hepatocellular carcinoma.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Iridoides/farmacología , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Antineoplásicos/química , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Glutatión/farmacología , Células Hep G2 , Humanos , Glucósidos Iridoides , Iridoides/química , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Gene therapy is a promising therapeutic approach for chemoresistant cervical cancers. Therapeutic interventions targeting the key factors contributing to the initiation and progression of cervical cancer may be a more effective treatment strategy. In the present study, we firstly determined the expression of protein tyrosine phosphatase receptor J (PTPRJ) in 8-paired human cervical tumor and non-tumor tissues. We observed a striking downregulation of PTPRJ in the human cervical tumor tissues. Next, we investigated the roles and the function mechanism of PTPRJ in the human cervical carcinoma cell line C33A by loss- and gain-of-function experiments. Our study indicated that C33A cells with loss of PTPRJ expression showed a significantly increased cell viability, rising growth and migration rate, as well as a G1-S transition. We obtained the opposite results when we overexpressed PTPRJ in C33A cells. Our further study indicated that PTPRJ levels were highly correlated with cell survival when the C33A cells were treated with 5-fluorouracil (5-FU), an important chemotherapeutic agent for cervical cancer. In addition, the signaling pathway screening assay showed an obvious alteration of the Janus kinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) pathway. PTPRJ negatively regulated the activation of the JAK1/STAT3 pathway by decreasing the phosphorylation levels of JAK1 and STAT3. In addition, PTPRJ also regulated the expression of the downstream factors of STAT3, such as cyclin D, Bax, VEGF and MMP2. Our results suggest that PTPRJ may be a promising gene therapy target and its therapeutic potential can be fulfilled when used alone, or in combination with other anticancer agents.
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Antimetabolitos Antineoplásicos/farmacología , Carcinoma/patología , Resistencia a Antineoplásicos/fisiología , Fluorouracilo/farmacología , Proteínas de Neoplasias/antagonistas & inhibidores , Procesamiento Proteico-Postraduccional , Transducción de Señal/fisiología , Proteínas Supresoras de Tumor/fisiología , Neoplasias del Cuello Uterino/patología , Carcinoma/enzimología , División Celular , Línea Celular Tumoral , Movimiento Celular , Activación Enzimática , Femenino , Puntos de Control de la Fase G1 del Ciclo Celular , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Células HEK293 , Humanos , Janus Quinasa 1 , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiología , Fosforilación , ARN Mensajero/biosíntesis , ARN Neoplásico/biosíntesis , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/antagonistas & inhibidores , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/biosíntesis , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/genética , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/fisiología , Proteínas Recombinantes de Fusión/metabolismo , Factor de Transcripción STAT3 , Proteínas Supresoras de Tumor/antagonistas & inhibidores , Proteínas Supresoras de Tumor/biosíntesis , Neoplasias del Cuello Uterino/enzimologíaRESUMEN
BACKGROUND & OBJECTIVE: Vertebral metastasis is a common manifestation of patients with advanced cancer without effective treatment. This study was to explore treatment value and efficacy of percutaneous vertebroplasty (PVP) combined with interventional chemotherapy on vertebral metastases. METHODS: Seventy-five patients with vertebral metastases (42 men, 33 women; aged 31-76 years) were divided into 2 groups: 39 were treated by PVP combined with chemotherapy (VPCC group), and 36 were treated by PVP alone (VP group). All procedures were guided by CT scan. The results and complications were evaluated by pain questionnaire and routine follow-up. RESULTS: Response rate was significantly higher in VPCC group than in VP group (93.0% vs. 74.4%, P < 0.05); complete response rates of VPCC group and VP group were 25.6% and 10.3%. Common complication of VPCC was transient aggravation of pain. CONCLUSIONS: PVP may release the pain, and consolidate the vertebrae of patients with vertebral metastases. Its short-term effect may be enhanced by adding drugs into bone cement.