RESUMEN
BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a lethal malignant tumour. Further study is needed to determine the molecular mechanism and identify novel biomarkers of PAAD. METHODS: Gene expression data from the GSE62165 microarray were analysed with the online software Morpheus to identify differentially expressed genes (DEGs). The STRING database was used to generate a proteinâprotein interaction (PPI) network for these DEGs. Hub genes were identified with Cytoscape. COL10A1 expression in PAAD was analysed via the GEPIA database. COL10A1 expression in pancreatic cancer cell lines was measured by using qRTâPCR. The LinkedOmics database was utilized to perform survival analysis of pancreatic adenocarcinoma patients grouped based on COL10A1 expression level. CCK-8, wound healing, and Transwell assays were used to study the role of COL10A1 in pancreatic cancer cell viability, migration, and invasion. Differentially expressed genes that were related to COL10A1 in PAAD were analysed via the LinkedOmics portal. After COL10A1 was knocked down, CD276 expression was assessed by western blotting. RESULTS: COL10A1 was identified as one of the hub genes in PAAD by bioinformatics analysis of the GSE62165 microarray with Morpheus, the STRING database and Cytoscape. GEPIA revealed elevated expression of COL10A1 in PAAD samples vs. normal samples. COL10A1 expression was also increased in pancreatic cancer cells vs. control cells. Survival analysis of PAAD patients via LinkedOmics revealed that high expression of COL10A1 was associated with a poorer prognosis. Knockdown of COL10A1 inhibited the proliferation, migration, and invasion of cells in functional assays. Furthermore, mechanistic studies indicated that CD276 was a target of COL10A1 and that knockdown of COL10A1 decreased CD276 expression. Overexpression of CD276 in cells reversed COL10A1 knockdown-induced repression of proliferation and migration. CONCLUSIONS: Our research suggests that COL10A1 promotes pancreatic adenocarcinoma tumorigenesis by regulating CD276. This study provides new insight into biomarkers and possible targets for pancreatic cancer treatment.
Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/genética , Antígenos B7 , Biomarcadores , Carcinogénesis/genética , Transformación Celular Neoplásica , Regulación Neoplásica de la Expresión Génica , Neoplasias Pancreáticas/genética , Pronóstico , Factores de Transcripción , Neoplasias PancreáticasRESUMEN
Postoperative cognitive dysfunction (POCD) is a well-known complication after surgery with cognitive impairments. Angiopoietin-like protein 2 (ANGPTL2) has been found to be associated with inflammation. However, the role of ANGPTL2 in inflammation of POCD is unclear. Here, mice were subjected into isoflurane anesthesia. It was demonstrated that isoflurane increased ANGPTL2 expression and promoted pathological change in brain tissues. However, downregulation of ANGPTL2 alleviated the pathological change and elevated learning and memory abilities, improving isoflurane-induced cognitive dysfunction in mice. In addition, isoflurane-induced cell apoptosis and inflammation were repressed via ANGPTL2 knockdown in mice. Downregulation of ANGPTL2 was also verified to suppress isoflurane-induced microglial activation, evidenced by a decrease of Iba1 and CD86 expressions and an increase of CD206 expression. Further, the isoflurane-induced MAPK signaling pathway was repressed through downregulation of ANGPTL2 in mice. In conclusion, this study proved that downregulation of ANGPTL2 attenuated isoflurane-induced neuroinflammation and cognitive dysfunction in mice via modulating the MAPK pathway, which provided a new therapeutic target for POCD.
Asunto(s)
Proteína 2 Similar a la Angiopoyetina , Disfunción Cognitiva , Isoflurano , Complicaciones Cognitivas Postoperatorias , Animales , Ratones , Proteína 2 Similar a la Angiopoyetina/genética , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Inflamación , Isoflurano/efectos adversos , Enfermedades NeuroinflamatoriasRESUMEN
BACKGROUND: The issue whether anaesthesia has an impact on the prognosis of carcinoma has been widely discussed and remains debated. Ropivacaine has been widely used in perioperative period as a long acting local anesthetic. An early event during recurrence or metastasis of carcinoma is the adhesion of circulating tumour cells (CTCs) to endothelial cells (ECs) through binding adhesion molecules that are up-regulated on inflamed endothelium during the perioperative period or other periods. This study was to explore the impact of ropivacaine on the adhesion of tumour cells, providing evidences of its influence on the prognosis of carcinoma. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were pre-treated with ropivacaine (10-7-10-5 M; 30 min) prior to treatment with tumour necrosis factor alpha (TNFα) (10 ng ml-1; 1, 4 and 8 h). Intercellular adhesion molecule-1 (ICAM-1), endothelial-selectin (CD62E) and vascular cell adhesion molecule-1 (VCAM-1) mRNA levels were detected via quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). To clarify the underlying action mechanism, p65, p-p65, IκBα, p-IκBα, IKKα/ß and p-IKKα/ß protein levels were evaluated via western blotting. Cell viability and tumour cell adhesion assays were also assessed. RESULTS: The clinically usage concentration of ropivacaine (10-6 M) produced a significant decrease in CD62E expression compared with that produced by TNFα only (p < 0.001). Moreover, adhesion assays showed that ropivacaine effectively inhibited the adhesion of hepatoma cells (p < 0.01), human colon cancer cells (p < 0.01) and human leukemic monocyte (p < 0.01). Western blot results showed that pre-treatment with ropivacaine inhibited the phosphorylation of p65 (p < 0.05), IκBα (p < 0.001) and IKKα/ß (p < 0.01). CONCLUSIONS: Ropivacaine decreased the adhesion of tumour cells. Ropivacaine modulated CD62E expression by inhibiting the activation of NF-κB. These results might provide new insight into the issue whether anaesthesia has an impact on the prognosis of carcinoma.