Open AccessMicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma
Author(s) -
Tainara F. Felix,
Rainer Marco López Lapa,
Marcelo Carvalho,
Natália Bertoni,
Tomáš Tokár,
Rogério Antônio de Oliveira,
Maria Aparecida Marchesan Rodrigues,
Cláudia Nishida Hasimoto,
Walmar Kerche de Oliveira,
Leonardo Pelafsky,
César Tadeu Spadella,
Juan Carlos Llanos,
Giovanni Faria Silva,
Wan L. Lam,
Sílvia Regina Rogatto,
Luciana Schultz,
Sandra A. Drigo,
Robson Francisco Carvalho,
Patrícia P. Reis
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0217421
Subject(s) - microrna , pancreatic cancer , biology , cancer research , immune system , innate immune system , adenocarcinoma , signal transduction , carcinogenesis , pancreas , acquired immune system , cancer , immunology , gene , endocrinology , microbiology and biotechnology , genetics
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 (FC≥2 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.