MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma

• Autor(a) principal: Felix, Tainara F. [UNESP]
• Data de Publicação: 2019
• Outros Autores: Lopez Lapa, Rainer M. [UNESP], De Carvalho, Márcio [UNESP], Bertoni, Natália [UNESP], Tokar, Tomas, Oliveira, Rogério A. [UNESP], Rodrigues, Maria A.M. [UNESP], Hasimoto, Cláudia N. [UNESP], Oliveira, Walmar K. [UNESP], Pelafsky, Leonardo [UNESP], Spadella, César T. [UNESP], Llanos, Juan C. [UNESP], Silva, Giovanni F. [UNESP], Lam, Wan L., Rogatto, Silvia Regina, Amorim, Luciana Schultz, Drigo, Sandra A. [UNESP], Carvalho, Robson F. [UNESP], Reis, Patricia P. [UNESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1371/journal.pone.0217421; http://hdl.handle.net/11449/189188

Despite progress in treatment strategies, only ~24% of pancreatic ductal adenocarcinoma (PDAC) patients survive >1 year. Our goal was to elucidate deregulated pathways modulated by microRNAs (miRNAs) in PDAC and Vater ampulla (AMP) cancers. Global miRNA expression was identified in 19 PDAC, 6 AMP and 25 paired, histologically normal pancreatic tissues using the GeneChip 4.0 miRNA arrays. Computational approaches were used for miRNA target prediction/identification of miRNA-regulated pathways. Target gene expression was validated in 178 pancreatic cancer and 4 pancreatic normal tissues from The Cancer Genome Atlas (TCGA). 20 miRNAs were significantly deregulated (FC2 and p<0.05) (15 down- and 5 up-regulated) in PDAC. miR-216 family (miR-216a-3p, miR-216a-5p, miR-216b-3p and miR-216b-5p) was consistently down-regulated in PDAC. miRNA-modulated pathways are associated with innate and adaptive immune system responses in PDAC. AMP cancers showed 8 down- and 1 up-regulated miRNAs (FDR p<0.05). Most enriched pathways (p<0.01) were RAS and Nerve Growth Factor signaling. PDAC and AMP display different global miRNA expression profiles and miRNA regulated networks/tumorigenesis pathways. The immune response was enriched in PDAC, suggesting the existence of immune checkpoint pathways more relevant to PDAC than AMP.