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Comprehensive Analysis of LincRNAs in Classical and Basal-Like Subtypes of Pancreatic Cancer

Pancreatic ductal adenocarcinomas (PDAC) belong to the deadliest malignancies in the western world. Mutations in TP53 and KRAS genes along with some other frequent polymorphisms occur almost universally and are major drivers of tumour initiation. However, these mutations cannot explain the heterogen...

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Autores principales: Glaß, Markus, Dorn, Agnes, Hüttelmaier, Stefan, Haemmerle, Monika, Gutschner, Tony
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464731/
https://www.ncbi.nlm.nih.gov/pubmed/32727085
http://dx.doi.org/10.3390/cancers12082077
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author Glaß, Markus
Dorn, Agnes
Hüttelmaier, Stefan
Haemmerle, Monika
Gutschner, Tony
author_facet Glaß, Markus
Dorn, Agnes
Hüttelmaier, Stefan
Haemmerle, Monika
Gutschner, Tony
author_sort Glaß, Markus
collection PubMed
description Pancreatic ductal adenocarcinomas (PDAC) belong to the deadliest malignancies in the western world. Mutations in TP53 and KRAS genes along with some other frequent polymorphisms occur almost universally and are major drivers of tumour initiation. However, these mutations cannot explain the heterogeneity in therapeutic responses and differences in overall survival observed in PDAC patients. Thus, recent classifications of PDAC tumour samples have leveraged transcriptome-wide gene expression data to account for epigenetic, transcriptional and post-transcriptional mechanisms that may contribute to this deadly disease. Intriguingly, long intervening RNAs (lincRNAs) are a special class of long non-coding RNAs (lncRNAs) that can control gene expression programs on multiple levels thereby contributing to cancer progression. However, their subtype-specific expression and function as well as molecular interactions in PDAC are not fully understood yet. In this study, we systematically investigated the expression of lincRNAs in pancreatic cancer and its molecular subtypes using publicly available data from large-scale studies. We identified 27 deregulated lincRNAs that showed a significant different expression pattern in PDAC subtypes suggesting context-dependent roles. We further analyzed these lincRNAs regarding their common expression patterns. Moreover, we inferred clues on their functions based on correlation analyses and predicted interactions with RNA-binding proteins, microRNAs, and mRNAs. In summary, we identified several PDAC-associated lincRNAs of prognostic relevance and potential context-dependent functions and molecular interactions. Hence, our study provides a valuable resource for future investigations to decipher the role of lincRNAs in pancreatic cancer.
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spelling pubmed-74647312020-09-04 Comprehensive Analysis of LincRNAs in Classical and Basal-Like Subtypes of Pancreatic Cancer Glaß, Markus Dorn, Agnes Hüttelmaier, Stefan Haemmerle, Monika Gutschner, Tony Cancers (Basel) Article Pancreatic ductal adenocarcinomas (PDAC) belong to the deadliest malignancies in the western world. Mutations in TP53 and KRAS genes along with some other frequent polymorphisms occur almost universally and are major drivers of tumour initiation. However, these mutations cannot explain the heterogeneity in therapeutic responses and differences in overall survival observed in PDAC patients. Thus, recent classifications of PDAC tumour samples have leveraged transcriptome-wide gene expression data to account for epigenetic, transcriptional and post-transcriptional mechanisms that may contribute to this deadly disease. Intriguingly, long intervening RNAs (lincRNAs) are a special class of long non-coding RNAs (lncRNAs) that can control gene expression programs on multiple levels thereby contributing to cancer progression. However, their subtype-specific expression and function as well as molecular interactions in PDAC are not fully understood yet. In this study, we systematically investigated the expression of lincRNAs in pancreatic cancer and its molecular subtypes using publicly available data from large-scale studies. We identified 27 deregulated lincRNAs that showed a significant different expression pattern in PDAC subtypes suggesting context-dependent roles. We further analyzed these lincRNAs regarding their common expression patterns. Moreover, we inferred clues on their functions based on correlation analyses and predicted interactions with RNA-binding proteins, microRNAs, and mRNAs. In summary, we identified several PDAC-associated lincRNAs of prognostic relevance and potential context-dependent functions and molecular interactions. Hence, our study provides a valuable resource for future investigations to decipher the role of lincRNAs in pancreatic cancer. MDPI 2020-07-27 /pmc/articles/PMC7464731/ /pubmed/32727085 http://dx.doi.org/10.3390/cancers12082077 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Glaß, Markus
Dorn, Agnes
Hüttelmaier, Stefan
Haemmerle, Monika
Gutschner, Tony
Comprehensive Analysis of LincRNAs in Classical and Basal-Like Subtypes of Pancreatic Cancer
title Comprehensive Analysis of LincRNAs in Classical and Basal-Like Subtypes of Pancreatic Cancer
title_full Comprehensive Analysis of LincRNAs in Classical and Basal-Like Subtypes of Pancreatic Cancer
title_fullStr Comprehensive Analysis of LincRNAs in Classical and Basal-Like Subtypes of Pancreatic Cancer
title_full_unstemmed Comprehensive Analysis of LincRNAs in Classical and Basal-Like Subtypes of Pancreatic Cancer
title_short Comprehensive Analysis of LincRNAs in Classical and Basal-Like Subtypes of Pancreatic Cancer
title_sort comprehensive analysis of lincrnas in classical and basal-like subtypes of pancreatic cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464731/
https://www.ncbi.nlm.nih.gov/pubmed/32727085
http://dx.doi.org/10.3390/cancers12082077
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