MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma.
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0217421 |
| _version_ | 1818682545015881728 |
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| author | Tainara F Felix Rainer M Lopez Lapa Márcio de Carvalho Natália Bertoni Tomas Tokar Rogério A Oliveira Maria A M Rodrigues Cláudia N Hasimoto Walmar K Oliveira Leonardo Pelafsky César T Spadella Juan C Llanos Giovanni F Silva Wan L Lam Silvia Regina Rogatto Luciana Schultz Amorim Sandra A Drigo Robson F Carvalho Patricia P Reis |
| author_facet | Tainara F Felix Rainer M Lopez Lapa Márcio de Carvalho Natália Bertoni Tomas Tokar Rogério A Oliveira Maria A M Rodrigues Cláudia N Hasimoto Walmar K Oliveira Leonardo Pelafsky César T Spadella Juan C Llanos Giovanni F Silva Wan L Lam Silvia Regina Rogatto Luciana Schultz Amorim Sandra A Drigo Robson F Carvalho Patricia P Reis |
| author_sort | Tainara F Felix |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T10:20:32Z |
| format | Article |
| id | doaj.art-3d6e9bf0128d46449f93a515a66dd786 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T10:20:32Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3d6e9bf0128d46449f93a515a66dd7862022-12-21T21:52:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01145e021742110.1371/journal.pone.0217421MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma.Tainara F FelixRainer M Lopez LapaMárcio de CarvalhoNatália BertoniTomas TokarRogério A OliveiraMaria A M RodriguesCláudia N HasimotoWalmar K OliveiraLeonardo PelafskyCésar T SpadellaJuan C LlanosGiovanni F SilvaWan L LamSilvia Regina RogattoLuciana Schultz AmorimSandra A DrigoRobson F CarvalhoPatricia P ReisDespite 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.https://doi.org/10.1371/journal.pone.0217421 |
| spellingShingle | Tainara F Felix Rainer M Lopez Lapa Márcio de Carvalho Natália Bertoni Tomas Tokar Rogério A Oliveira Maria A M Rodrigues Cláudia N Hasimoto Walmar K Oliveira Leonardo Pelafsky César T Spadella Juan C Llanos Giovanni F Silva Wan L Lam Silvia Regina Rogatto Luciana Schultz Amorim Sandra A Drigo Robson F Carvalho Patricia P Reis MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma. PLoS ONE |
| title | MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma. |
| title_full | MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma. |
| title_fullStr | MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma. |
| title_full_unstemmed | MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma. |
| title_short | MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma. |
| title_sort | microrna modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma |
| url | https://doi.org/10.1371/journal.pone.0217421 |
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