Altered transcriptional regulatory proteins in glioblastoma and YBX1 as a potential regulator of tumor invasion

Abstract

We have studied differentially regulated nuclear proteome of the clinical tissue specimens of glioblastoma (GBM, WHO Grade IV) and lower grades of gliomas (Grade II and III) using high resolution mass spectrometry- based quantitative proteomics approach. The results showed altered expression of many regulatory proteins from the nucleus such as DNA binding proteins, transcription and post transcriptional processing factors and also included enrichment of nuclear proteins that are targets of granzyme signaling – an immune surveillance pathway. Protein - protein interaction network analysis using integrated proteomics and transcriptomics data of transcription factors and proteins for cell invasion process (drawn from another GBM dataset) revealed YBX1, a ubiquitous RNA and DNA-binding protein and a transcription factor, as a key interactor of major cell invasion-associated proteins from GBM. To verify the regulatory link between them, the co-expression of YBX1 and six of the interacting proteins (EGFR, MAPK1, CD44, SOX2, TNC and MMP13) involved in cell invasion network was examined by immunohistochemistry on tissue micro arrays. Our analysis suggests YBX1 as a potential regulator of these key molecules involved in tumor invasion and thus as a promising target for development of new therapeutic strategies for GBM.

A Five-lncRNAs Signature-Derived Risk Score Based on TCGA and CGGA for Glioblastoma: Potential Prospects for Treatment Evaluation and Prognostic Prediction

“…In order to confirm the accuracy of gene screening, we predicted the target proteins of the 5 lncRNAs (Tables S1-S3), and conducted an interaction network analysis of the proteins ( Figure S2). Finding that TBX5-AS1 may be related to some oncogenic protein (15)(16)(17)(18), while the other 4 lncRNAs may be associated to some tumor suppressor proteins (19)(20)(21)(22). Indicating that these lncRNAs may be key genes in GBM.…”

Spatial-transcriptomics reveals unique defining molecular features of fluorescence-sorted 5-aminolevulinic acid+ infiltrative tumor cells associated with glioblastoma recurrence and poor survival

“…Upregulation of exonic levels for MES and inflammatory wound-response genes in 5ALA+ relative to 5ALA-cells implied that these genes were under active post-transcriptional control. Previously, a mass-spectrometry-based study has shown that altered expression of nuclear regulatory proteins controlling transcription and post-transcriptional processes may drive GBM invasion 54 . In addition to the differential abundance of nuclear proteins, the role of the microenvironment in the regulation of post-transcriptional processes including splicing and translational control cannot be ruled out 55 .…”

Spatial-transcriptomics reveals unique defining molecular features of 5-aminolevulinic acid+ infiltrative tumor cells associated with glioblastoma recurrence and poor survival

“…Upregulation of exonic levels for MES and Inflammatory wound-response genes in 5ALA+ relative to 5ALA-cells implied that these genes were under active posttranscriptional control. Previously, a mass-spectrometry-based study has shown that altered expression of nuclear regulatory proteins controlling transcription and posttranscriptional processes may drive GBM invasion 31 . In addition to the differential abundance of nuclear proteins, the role of the microenvironment in the regulation of post-transcriptional processes including splicing and translational control cannot be ruled out 32 .…”