RESUMO
OBJECTIVE: Rap1GAP is considered a tumor suppressor gene, but its regulatory mechanism in papillary thyroid cancer (PTC) has not been clearly elucidated. The aim of this study was to explore whether the regulation between Rap1GAP and sodium/iodine transporter (NIS) in tumorigenesis of PTC is mediated by TGF-ß1. METHODS: Western blotting (WB) and quantitative reverse-transcription polymerase chain reaction were performed to analyze the relationships between TGF-ß1 concentration and NIS expression. After transfecting BCPAP cells with siRNAs, the Rap1GAP interference model was successfully established. Then, the expression and nuclear localization of TGF-ß1 and pathway-related proteins were detected. Flow cytometry was applied to analyze cell apoptosis and cycle. WB was performed to detect apoptotic-related proteins. Wound healing and transwell assays were used to measure cell migration and invasion. EDU was performed to detect cell proliferative activity. RESULTS: The results suggested that TGF-ß1 could significantly inhibit the expression of NIS in both mRNA and protein levels. In BCPAP cells transfected with siRNA-Rap1GAP, the expression levels of TGF-ß1, Foxp3, and p-Smad3 were significantly increased. By applying immunofluorescence assay, the nuclear localizations of TßR-1 and p-Smad3 were found to be activated. Moreover, anti-TGF-ß1 can reverse the decrease in NIS expression caused by downregulation of Rap1GAP. Additionally, the knockdown of Rap1GAP could alter the cell apoptosis, cycle, migration, invasion, and proliferation of BCPAP. CONCLUSION: The downregulation of Rap1GAP expression can activate the TGF-ß/Smad3 pathway to inhibit NIS expression and alter the tumor cell functions of PTC.
Assuntos
Proteínas Ativadoras de GTPase/metabolismo , Proteína Smad3/metabolismo , Simportadores/metabolismo , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Feminino , Proteínas Ativadoras de GTPase/antagonistas & inibidores , Proteínas Ativadoras de GTPase/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Transdução de Sinais , Simportadores/antagonistas & inibidores , Simportadores/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologiaRESUMO
BACKGROUND: Pancreatic cancer remains one of the most lethal cancers. OBJECTIVE: This study aimed to analyze T cell-related biomarkers and their molecular network in pancreatic cancer. METHODS: RNAseq sequencing data and clinical data of pancreatic cancer were obtained from TCGA database. The STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE) algorithm was used to screen the DEGs related to the tumor immune cells. The pearson correlation analysis were used to analyze the relationships between DEGs and T cells. Additionally, the T cell-related DEGs were subjected to protein-protein interaction, competing endogenous RNA (ceRNA), and chemical small molecule-target network construction. Furthermore, the prognosis-associated DEGs were screened. RESULTS: A total of 412 stromal score-associated and 312 immune score-associated DEGs were obtained. From these DEGs, 50 CD4+ T cell-related genes and 13 CD8+ T cell-related genes were selected. The PPI networks associated with immune cell-related genes were constructed and found that CD22, SELL, and OLR1 had higher degrees in the PPI network. The number of ceRNA regulatory relation pairs obtained from CD4+ T cells and CD8+ T cells were 59 and 48, respectively. Additionally, both CD4+ T cell- and CD8+ T cell-related genes predicted 29 small molecules. CXCL9 and GIMAP7 were screened out from CD4+ T cell-related genes, which were related with the survival of pancreatic cancer. CONCLUSION: We mapped T cell-related gene profile in pancreatic cancer and constructed their potential regulatory network.
Assuntos
Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Algoritmos , Biomarcadores Tumorais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Quimiocina CXCL9/genética , Feminino , Proteínas de Ligação ao GTP/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , RNA Neoplásico/genética , Análise de SobrevidaRESUMO
BACKGROUND: The gut microbiome changes are related to the colorectal cancer (CRC). Chemotherapy is one of the main treatment methods for CRC. PURPOSE: To explore the effect of chemotherapy on the gut bacteria and fungi in CRC. METHODS: Total of 11 advanced CRC patients treated with the FOLFIRI regimen, 15 postoperative CRC patients treated with the XELOX regimen, and corresponding CRC patients without surgery and chemotherapy were recruited. The 16S ribosomal RNA and ITS sequences were sequenced, and bioinformatics analysis was executed to screen for the distinctive gut microbiome. RESULTS: The abundances of Veillonella, Humicola, Tremellomycetes and Malassezia were increased in postoperative CRC patients treated with the XELOX regimen. The abundances of Faecalibacterium, Clostridiales, phascolarctobacterium, Humicola and Rhodotorula were decreased, and the abundances of Candida, Magnusiomyces, Tremellomycetes, Dipodascaceae, Saccharomycetales, Malassezia and Lentinula were increased in advanced CRC patients treated with the FOLFIRI regimen. The abundances of Humicola, Rhodotorula, and Magnusiomyces were decreased, and the abundances of Candida, Tremellomycetes, Dipodascaceae, Saccharomycetales, Malassezia and Lentinula were increased in advanced CRC patients treated with the FOLFIRI regimen combined with cetuximab compared with those treated with the FOLFIRI regimen alone. CONCLUSIONS: The community structure of gut bacteria and fungi changes in chemotherapy on CRCs.