RESUMO
PURPOSE: To explore the altered different expression of miRNAs and the mechanisms underlying the relapse and metastasis of pancreatic cancer. MATERIALS AND METHODS: The most differentially expressed miRNAs were analyzed by gene ontology (GO) term analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein interaction analysis. The potentially regulated target genes of the most differentially expressed miRNAs were also analyzed further by GO term analysis and KEGG pathway analysis, and quantitated by qRT-PCR. RESULTS: In total, we found 12 miRNAs displayed at least a 30-fold increase or decrease in expression of carcinoma and relapse vs. para-carcinoma human pancreatic cancer (C/R vs. P). In addition, our study found that pancreatic cancer was related to pathways in cancer, including Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway. CONCLUSIONS: The differential expressed miRNAs and their predicted target genes that involved in Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway indicating their potential roles in pancreatic carcinogenesis and progress.
Assuntos
Carcinoma/genética , MicroRNAs/genética , Recidiva Local de Neoplasia/genética , Neoplasias Pancreáticas/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Janus Quinases/genética , Sistema de Sinalização das MAP Quinases , Análise de Sequência com Séries de Oligonucleotídeos , Pâncreas/química , Receptores Ativados por Proliferador de Peroxissomo/genética , Fatores de Transcrição STAT/genética , Transcriptoma , Regulação para CimaRESUMO
Arabidopsis (Arabidopsis thaliana) group A1 heat shock factors (Hsfs), including HsfA1a, are important regulators in the heat shock response. Previous studies have revealed that genetically engineered HsfA1 members result in constitutive Hsf activation and heat shock protein gene (Hsp) expression under normal conditions, eventually enhancing basic thermotolerance in transgenic plants. In this study, we generated transgenic Arabidopsis plants overexpressing HsfA1a. One transgenic line showed a 94-fold increase in the level of HsfA1a mRNA (OE line 1). Overexpressing HsfA1a in OE line 1 plants resulted in higher levels of the inducible expression of Hsp18.2 and Hsp70 genes in response to heat stress, low/high pH changes, and hydrogen peroxide. Analysis of in vivo HsfA1a-promoter binding suggested that the higher level of inducible Hsp expression was mediated by stress-induced activation of elevated levels of HsfA1a in the OE plants. The OE plants showed an increase in tolerance to low/ high pH changes and hydrogen peroxide, in addition to heat shock. These results revealed that overexpressing HsfA1a had positive effects on tolerance to diverse stressors by promoting inducible Hsp expression following stress-induced HsfA1a activation. This study suggests a different mechanism for the activation of genetically engineered Hsfs from that suggested in previous reports, thus providing new insight into complex mechanisms used for achieving stress tolerance by genetic engineering.