AUTHOR=Mukherjee Moumita , Goswami Srikanta 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.713852

DOI=10.3389/fcell.2021.713852

ISSN=2296-634X

ABSTRACT=RNA Binding Proteins (RBPs) play 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 tumours and 124 normal pancreatic tissues, performed a meta-analysis and obtained differentially expressed RBPs (DE-RBPs) using 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 done using DE-RBPs and we also constructed 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 tumour 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 tumour cell migration and metastasis in pancreatic cancer. IGF2BP3, ISG20, NIP7, PRDX1, RCC2, RUVBL1, SNRPD1, PAIP2B and SIDT2 were found to play most prominent role in regulation of EMT in the process. The findings not only contribute to understand the biology of RBPs in pancreatic cancer but also evaluate their candidature as possible therapeutic targets.