Integrated Analysis of RNA-Binding Proteins in Glioma

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.

Age and Sex-Related Changes in Human First-Trimester Placenta Transcriptome and Insights into Adaptative Responses to Increased Oxygen

“…With respect to this kind of analysis, the Limma, edgeR or DESeq2 methods represent improvements over Student’s test, but ignore the data connections in the matrix that arise as a result of topology [ 31 ]. To address these limitations, our analysis followed the example of several previous studies [ 32 , 33 , 34 , 35 ] and combined the methods of DESeq2 and WGCNA.…”

Development and Multi-Data Set Verification of an RNA Binding Protein Signature for Prognosis Prediction in Glioma

“…In line with the 2016 World Health Organization (WHO) classification, glioblastoma (GBM) is the most common histology type, which corresponds to WHO grade IV, with a median survival of <2 years and a 5-year survival rate of 5% ( 2 ). The incidence of lower grade gliomas (LGG) WHO grade II is relatively lower and patients with grade II exhibit better clinical outcomes and more sensitive to therapies ( 3 ). At present, the diagnosis of glioma primarily depends on histopathology, imaging as well as molecular diagnosis ( 4 – 6 ).…”

Identification of Prognosis-related Hub RNA Binding Proteins Function through Regulating Metabolic Processes in Tongue Cancer

“…RNA binding proteins (RBPs) are a class of proteins that interacting with a variety type of RNAs. To date, more than 3800 human RBPs were determined in diverse cell types [9][10][11][12]. These RBPs…”

“…RNA binding proteins (RBPs) are a class of proteins that interacting with a variety type of RNAs. To date, more than 3800 human RBPs were determined in diverse cell types 9 - 12 . These RBPs establish highly dynamic interactions with other proteins, coding and/or noncoding RNAs, and influence a variety of physiological and pathological processes including cancer 13 .…”