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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Main Authors: Markus Glaß, Agnes Dorn, Stefan Hüttelmaier, Monika Haemmerle, Tony Gutschner
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/12/8/2077
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author Markus Glaß
Agnes Dorn
Stefan Hüttelmaier
Monika Haemmerle
Tony Gutschner
author_facet Markus Glaß
Agnes Dorn
Stefan Hüttelmaier
Monika Haemmerle
Tony Gutschner
author_sort Markus Glaß
collection DOAJ
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 doaj.art-1a63cc6dcd004d17bdfad70bb97a460f2023-11-20T08:07:01ZengMDPI AGCancers2072-66942020-07-01128207710.3390/cancers12082077Comprehensive Analysis of LincRNAs in Classical and Basal-Like Subtypes of Pancreatic CancerMarkus Glaß0Agnes Dorn1Stefan Hüttelmaier2Monika Haemmerle3Tony Gutschner4Institute of Molecular Medicine, Section for Cell Biology, Medical Faculty, Martin-Luther University Halle-Wittenberg, 06120 Halle/Saale, GermanyInstitute of Pathology, Section for Experimental Pathology, Medical Faculty, Martin-Luther University Halle-Wittenberg, 06120 Halle/Saale, GermanyInstitute of Molecular Medicine, Section for Cell Biology, Medical Faculty, Martin-Luther University Halle-Wittenberg, 06120 Halle/Saale, GermanyInstitute of Pathology, Section for Experimental Pathology, Medical Faculty, Martin-Luther University Halle-Wittenberg, 06120 Halle/Saale, GermanyJunior Research Group ‘RNA Biology and Pathogenesis’, Medical Faculty, Martin-Luther University Halle-Wittenberg, 06120 Halle/Saale, GermanyPancreatic 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.https://www.mdpi.com/2072-6694/12/8/2077cancerlincRNAlncRNAmiRNApancreatic ductal adenocarcinomaRBP
spellingShingle Markus Glaß
Agnes Dorn
Stefan Hüttelmaier
Monika Haemmerle
Tony Gutschner
Comprehensive Analysis of LincRNAs in Classical and Basal-Like Subtypes of Pancreatic Cancer
Cancers
cancer
lincRNA
lncRNA
miRNA
pancreatic ductal adenocarcinoma
RBP
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 cancer
lincRNA
lncRNA
miRNA
pancreatic ductal adenocarcinoma
RBP
url https://www.mdpi.com/2072-6694/12/8/2077
work_keys_str_mv AT markusglaß comprehensiveanalysisoflincrnasinclassicalandbasallikesubtypesofpancreaticcancer
AT agnesdorn comprehensiveanalysisoflincrnasinclassicalandbasallikesubtypesofpancreaticcancer
AT stefanhuttelmaier comprehensiveanalysisoflincrnasinclassicalandbasallikesubtypesofpancreaticcancer
AT monikahaemmerle comprehensiveanalysisoflincrnasinclassicalandbasallikesubtypesofpancreaticcancer
AT tonygutschner comprehensiveanalysisoflincrnasinclassicalandbasallikesubtypesofpancreaticcancer