Integrated Analysis of RNA-Binding Proteins in Glioma.

Zhixing Wang,Wanjun Tang,Boqin Qiang,Xiaozhong Peng,Jiangang Yuan,Wei Han

doi:10.3390/cancers12040892

Zhixing Wang, Wanjun Tang + Show 4 more

Open Access

https://doi.org/10.3390/cancers12040892

Copy DOI

Abstract

RNA-binding proteins (RBPs) play important roles in many cancer types. However, RBPs have not been thoroughly and systematically studied in gliomas. Global analysis of the functional impact of RBPs will provide a better understanding of gliomagenesis and new insights into glioma therapy. In this study, we integrated a list of the human RBPs from six sources—Gerstberger, SONAR, Gene Ontology project, Poly(A) binding protein, CARIC, and XRNAX—which covered 4127 proteins with RNA-binding activity. The RNA sequencing data were downloaded from The Cancer Genome Atlas (TCGA) (n = 699) and Chinese Glioma Genome Atlas (CGGA) (n = 325 + 693). We examined the differentially expressed genes (DEGs) using the R package DESeq2, and constructed a weighted gene co-expression network analysis (WGCNA) of RBPs. Furthermore, survival analysis was also performed based on the univariate and multivariate Cox proportional hazards regression models. In the WGCNA analysis, we identified a key module involved in the overall survival (OS) of glioblastomas. Survival analysis revealed eight RBPs (PTRF, FNDC3B, SLC25A43, ZC3H12A, LRRFIP1, HSP90B1, HSPA5, and BNC2) are significantly associated with the survival of glioblastoma patients. Another 693 patients within the CGGA database were used to validate the findings. Additionally, 3564 RBPs were classified into canonical and non-canonical RBPs depending on the domains that they contain, and non-canonical RBPs account for the majority (72.95%). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that some non-canonical RBPs may have functions in glioma. Finally, we found that the knockdown of non-canonical RBPs, PTRF, or FNDC3B can alone significantly inhibit the proliferation of LN229 and U251 cells. Simultaneously, RNA Immunoprecipitation (RIP) analysis indicated that PTRF may regulate cell growth and death- related pathways to maintain tumor cell growth. In conclusion, our findings presented an integrated view to assess the potential death risks of glioblastoma at a molecular level, based on the expression of RBPs. More importantly, we identified non-canonical RNA-binding proteins PTRF and FNDC3B, showing them to be potential prognostic biomarkers for glioblastoma.

Highlights

RNA-binding proteins (RBPs) are inherently pleiotropic proteins, regulating gene expression at the post-transcriptional level by interacting with target RNAs [1,2,3]
We comprehensively analyzed the key RBPs modules associated with the overall survival of glioma using bioinformatics analysis
The survival analysis revealed that a cluster of RBPs might have a prognostic value for GBM

Summary

Introduction

RNA-binding proteins (RBPs) are inherently pleiotropic proteins, regulating gene expression at the post-transcriptional level by interacting with target RNAs [1,2,3]. RNA-binding proteins are involved in RNA metabolism [4] and play vital roles in regulating RNA stability, alternative splicing, modification, location, and translation [5]. RNA-binding domains (RBDs) are the regions of RBPs that have been experimentally or structurally confirmed to bind RNAs directly [1]. Proteins containing RBDs are called classical or canonical RBPs. some RNA-binding proteins have not been proved to have the established domains by direct experimental evidence. We temporarily called them non-classical or non-canonical RBPs. Over the past few decades, it has been reported that some metabolic enzymes have RNA-binding abilities and can regulate the expression of their target

Methods

Results

Discussion

Conclusion