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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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.713852/full |
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| author | Moumita Mukherjee Srikanta Goswami Srikanta Goswami |
| author_facet | Moumita Mukherjee Srikanta Goswami Srikanta Goswami |
| author_sort | Moumita Mukherjee |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T14:34:15Z |
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| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-14T14:34:15Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-80ed6fb03f9a4855b4c5b9cb637632fc2022-12-21T22:57:44ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-11-01910.3389/fcell.2021.713852713852Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of OncogenesisMoumita Mukherjee0Srikanta Goswami1Srikanta Goswami2National Institute of Biomedical Genomics, Kalyani, IndiaNational Institute of Biomedical Genomics, Kalyani, IndiaRegional Centre for Biotechnology, Faridabad, IndiaRNA-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.https://www.frontiersin.org/articles/10.3389/fcell.2021.713852/fullRNA-binding proteinpancreatic cancermeta-analysisepithelial-to-mesenchymal transitiontarget RNAs |
| spellingShingle | 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 Frontiers in Cell and Developmental Biology RNA-binding protein pancreatic cancer meta-analysis epithelial-to-mesenchymal transition target RNAs |
| title | 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_short | 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 |
| topic | RNA-binding protein pancreatic cancer meta-analysis epithelial-to-mesenchymal transition target RNAs |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.713852/full |
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