Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis

RNA-binding proteins (RBPs) play a significant role in multiple cellular processes with their deregulations strongly associated with cancer. However, there are not adequate evidences regarding global alteration and functions of RBPs in pancreatic cancer, interrogated in a systematic manner. In this...

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Autores principales:	Moumita Mukherjee, Srikanta Goswami
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	RNA-binding protein pancreatic cancer meta-analysis epithelial-to-mesenchymal transition target RNAs Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/80ed6fb03f9a4855b4c5b9cb637632fc
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spelling	oai:doaj.org-article:80ed6fb03f9a4855b4c5b9cb637632fc2021-12-01T14:05:42ZIdentification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis2296-634X10.3389/fcell.2021.713852https://doaj.org/article/80ed6fb03f9a4855b4c5b9cb637632fc2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.713852/fullhttps://doaj.org/toc/2296-634XRNA-binding proteins (RBPs) play a significant role in multiple cellular processes with their deregulations strongly associated with cancer. However, there are not adequate evidences regarding global alteration and functions of RBPs in pancreatic cancer, interrogated in a systematic manner. In this study, we have prepared an exhaustive list of RBPs from multiple sources, downloaded gene expression microarray data from a total of 241 pancreatic tumors and 124 normal pancreatic tissues, performed a meta-analysis, and obtained differentially expressed RBPs (DE-RBPs) using the Limma package of R Bioconductor. The results were validated in microarray datasets and the Cancer Genome Atlas (TCGA) RNA sequencing dataset for pancreatic adenocarcinoma (PAAD). Pathway enrichment analysis was performed using DE-RBPs, and we also constructed the protein–protein interaction (PPI) network to detect key modules and hub-RBPs. Coding and noncoding targets for top altered and hub RBPs were identified, and altered pathways modulated by these targets were also investigated. Our meta-analysis identified 45 upregulated and 15 downregulated RBPs as differentially expressed in pancreatic cancer, and pathway enrichment analysis demonstrated their important contribution in tumor development. As a result of PPI network analysis, 26 hub RBPs were detected and coding and noncoding targets for all these RBPs were categorized. Functional exploration characterized the pathways related to epithelial-to-mesenchymal transition (EMT), cell migration, and metastasis to emerge as major pathways interfered by the targets of these RBPs. Our study identified a unique meta-signature of 26 hub-RBPs to primarily modulate pancreatic tumor cell migration and metastasis in pancreatic cancer. IGF2BP3, ISG20, NIP7, PRDX1, RCC2, RUVBL1, SNRPD1, PAIP2B, and SIDT2 were found to play the most prominent role in the regulation of EMT in the process. The findings not only contribute to understand the biology of RBPs in pancreatic cancer but also to evaluate their candidature as possible therapeutic targets.Moumita MukherjeeSrikanta GoswamiSrikanta GoswamiFrontiers Media S.A.articleRNA-binding proteinpancreatic cancermeta-analysisepithelial-to-mesenchymal transitiontarget RNAsBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	RNA-binding protein pancreatic cancer meta-analysis epithelial-to-mesenchymal transition target RNAs Biology (General) QH301-705.5
spellingShingle	RNA-binding protein pancreatic cancer meta-analysis epithelial-to-mesenchymal transition target RNAs Biology (General) QH301-705.5 Moumita Mukherjee Srikanta Goswami Srikanta Goswami Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis
description	RNA-binding proteins (RBPs) play a significant role in multiple cellular processes with their deregulations strongly associated with cancer. However, there are not adequate evidences regarding global alteration and functions of RBPs in pancreatic cancer, interrogated in a systematic manner. In this study, we have prepared an exhaustive list of RBPs from multiple sources, downloaded gene expression microarray data from a total of 241 pancreatic tumors and 124 normal pancreatic tissues, performed a meta-analysis, and obtained differentially expressed RBPs (DE-RBPs) using the Limma package of R Bioconductor. The results were validated in microarray datasets and the Cancer Genome Atlas (TCGA) RNA sequencing dataset for pancreatic adenocarcinoma (PAAD). Pathway enrichment analysis was performed using DE-RBPs, and we also constructed the protein–protein interaction (PPI) network to detect key modules and hub-RBPs. Coding and noncoding targets for top altered and hub RBPs were identified, and altered pathways modulated by these targets were also investigated. Our meta-analysis identified 45 upregulated and 15 downregulated RBPs as differentially expressed in pancreatic cancer, and pathway enrichment analysis demonstrated their important contribution in tumor development. As a result of PPI network analysis, 26 hub RBPs were detected and coding and noncoding targets for all these RBPs were categorized. Functional exploration characterized the pathways related to epithelial-to-mesenchymal transition (EMT), cell migration, and metastasis to emerge as major pathways interfered by the targets of these RBPs. Our study identified a unique meta-signature of 26 hub-RBPs to primarily modulate pancreatic tumor cell migration and metastasis in pancreatic cancer. IGF2BP3, ISG20, NIP7, PRDX1, RCC2, RUVBL1, SNRPD1, PAIP2B, and SIDT2 were found to play the most prominent role in the regulation of EMT in the process. The findings not only contribute to understand the biology of RBPs in pancreatic cancer but also to evaluate their candidature as possible therapeutic targets.
format	article
author	Moumita Mukherjee Srikanta Goswami Srikanta Goswami
author_facet	Moumita Mukherjee Srikanta Goswami Srikanta Goswami
author_sort	Moumita Mukherjee
title	Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis
title_short	Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis
title_full	Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis
title_fullStr	Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis
title_full_unstemmed	Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis
title_sort	identification of key deregulated rna-binding proteins in pancreatic cancer by meta-analysis and prediction of their role as modulators of oncogenesis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/80ed6fb03f9a4855b4c5b9cb637632fc
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_version_	1718405069238435840

Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis

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