RESUMO
Six-Transmembrane Epithelial Antigene of the Prostate 1 (STEAP1) is associated with the occurrence and development of cancer. This study aimed to clarify the role of STEAP1 in gastric cancer tumour growth and metastasis, as well as its molecular mechanism of action.Statistical methods were used for clinical data analysis. Protein expression was detected using immunohistochemistry(IHC). The mRNA and protein expression in the cell cultures were detected using reverse transcription-polymerase chain reaction(RT-PCR) and western blot analysis. Overexpression and silencing models were constructed using plasmid and lentivirus transfection. To detect cell proliferation in vitro, Cell Counting Kit-8(CCK-8), flow cytometry and colony formation assays were used; transwell and wound healing assays were used to detect cell migration and invasion;For in vivo experiments, nude BALB/c mice were used for detecting subcutaneous tumorigenesis and intraperitoneal implantation. In the results,we found STEAP1 was overexpressed in gastric cancer tissues and cell lines. Single-factor and Cox analyses showed that STEAP1 gene expression level correlated with poor prognosis. Up-regulation of STEAP1 increased cell proliferation, migration and invasion, which decreased after STEAP1 was knocked down. These changes were achieved via the activation of the AKT/FoxO1 pathway and epithelial-mesenchymal transformation (EMT). The in vivo animal experiments showed that STEAP1 knock down, resulted in a decrease in the subcutaneous tumour and peritoneal tumour formation.
Assuntos
Antígenos de Neoplasias/genética , Biomarcadores Tumorais , Oxirredutases/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Animais , Antígenos de Neoplasias/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/genética , Feminino , Expressão Gênica , Xenoenxertos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Oxirredutases/metabolismo , Prognóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Carga TumoralRESUMO
PURPOSE: To investigate lipase C hepatic type (LIPC) expression in Borrmann type 4 gastric cancer and its correlation with clinical outcome. The biological roles of LIPC in Borrmann type 4 gastric cancer progression were also investigated. METHODS: We determined LIPC expression in 324 primary gastric cancer tissues and 178 matched adjacent non-tumor tissues by immunohistochemistry. We explored the role of LIPC in Borrmann type 4 gastric cancer cell (OCUM-1) migration, invasion, proliferation, cell cycle, and expression of epithelial-mesenchymal transition-related genes by knocking down LIPC expression. RESULTS: LIPC expression was upregulated in Borrmann type 4 gastric cancer tissues compared with other types of gastric cancer and adjacent non-tumor tissues. High LIPC expression correlated with lymph node metastasis, advanced TNM stage, and poor overall survival in Borrmann type 4 gastric cancer patients. Multivariate analysis demonstrated that high LIPC expression was an independent prognostic factor in patients with Borrmann type 4 gastric cancer. By reducing LIPC expression, OCUM-1 cell invasion and migration were suppressed and Snail and MMP2 expression was downregulated, while E-cadherin expression was upregulated. CONCLUSIONS: High LIPC expression correlates with poor clinical outcome and plays an important role in regulating cell migration and invasion in Borrmann type 4 gastric cancer.
Assuntos
Neoplasias Gástricas , Humanos , Imuno-Histoquímica , Metástase Linfática , Fenótipo , Prognóstico , Neoplasias Gástricas/genéticaRESUMO
Although the anomalous expression of long non-coding RNAs (lncRNAs) has been extensively investigated in numerous carcinomas including gastric cancer (GC), their function remains unclear. The aim of our study was to explore the role of LINC01235 in GC. We used real-time quantitative PCR (RT-qPCR) to measure the expression of LINC01235 and twist family bHLH transcription factor 2 (TWIST2) in GC tissues. Scratch and transwell assays were performed to evaluate cellular capacity for migration and invasion. Gene relationships were explored by Weighted Gene Co-Expression Network Analysis (WGCNA). We measured TWIST2, thrombospondin 2 (THBS2) and epithelial-mesenchymal transition (EMT)-related proteins with western blot. We also used Pearson correlation analysis and the Kaplan-Meier method to detect associations among genes and overall survival. We found that LINC01235 was upregulated in GC tissues and cells. LINC01235 down-regulation restricted migration and invasion. Interestingly, we found the LINC01235-TWIST2-THBS2 axis induced EMT. Additionally, TWIST2 upregulated LINC01235 transcription in luciferase and chromatin immunoprecipitation (ChIP) assays. Bioinformatics analysis showed that microRNA (miR)-6852-5p might be a key gene involved in the regulation of TWIST2 by LINC01235. The LINC01235-TWIST2 positive feedback loop mainly affected migration and invasion of GC cells, which suggests it may serve as a potential therapeutic target in gastric cancer.
Assuntos
Carcinoma/genética , Transição Epitelial-Mesenquimal/genética , Proteínas Repressoras/genética , Neoplasias Gástricas/genética , Trombospondinas/genética , Proteína 1 Relacionada a Twist/genética , Idoso , Animais , Antígenos CD/genética , Caderinas/genética , Carcinoma/patologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Retroalimentação Fisiológica , Feminino , Fibronectinas/genética , Técnicas de Silenciamento de Genes , Humanos , Pulmão , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Transplante de Neoplasias , RNA Longo não Codificante/genética , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/patologia , Trombospondinas/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Vimentina/genéticaRESUMO
Background: We integrated changes in the trends in clinicopathologic characteristics and postoperative prognosis in patients with gastric cancer Northern China over a 30-year period. Methods: A retrospective analysis of patients undergoing gastric cancer resection and complete follow-up information from January 1981 to December 2010 in the first affiliated Hospital of China Medical University was carried out. We divided the patients into three consecutive periods. Results: A total of 3,520 patients were included in this study. The proportion of lower tumors increased (from 58.8 to 66.9%), while that of upper tumors decreased (from 21.3 to 13.4%). The proportion of tumors > 5cm decreased (from 58.6 to 41.1 %), but the increasing trend of poorly differentiated gastric cancer was obvious (from 60.1 to 75.7%). The percentage of early gastric cancer increased from 10.0 to 15.5 during the study periods, and that of TNM stage â £ cancer decreased from 38.6 to 28.1. In surgery treatment, the rate of radical resection increased to 92.1% in recent period, and the average number of retrieved lymph nodes increased. The 5-year survival rate gradually increased from 36.5% to 48.5% (p<0.001). The Multivariate analysis showed that age, tumor size, T stage, N stage, number of retrieved lymph nodes and resection type were independent prognostic factors for gastric cancer. Conclusion: The patterns of clinicopathologic features for gastric cancer changed during the 30-year period in North China. Overall survival (OS) could be increased by early detection of tumors and standard surgical treatment.