Proteo-transcriptomics meta-analysis identifies SUMO2 as a promising target in glioblastoma multiforme therapeutics

Abstract Background Glioblastoma multiforme (GBM) is a deadly brain tumour with minimal survival rates due to the ever-expanding heterogeneity, chemo and radioresistance. Kinases are known to crucially drive GBM pathology; however, a rationale therapeutic combination that can simultaneously inhibit...

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Bibliographic Details
Published inCancer cell international Vol. 21; no. 1; pp. 1 - 16
Main Authors Krishna, Aswani P., John, Sebastian, Shinde, Puja Laxmanrao, Mishra, Rashmi
Format Journal Article
LanguageEnglish
Published London BioMed Central 29.10.2021
BMC
Subjects
Algorithms
Bioinformatics
Brain cancer
Brain tumors
Cancer drug target discovery
Cell cycle
Cell division
Cyclin-dependent kinases
DNA repair
Drug therapy
Genes
Glioblastoma
Glioblastoma multiforme
Hypothesis
Isoforms
Kinases
Kinases and cancer
Macrophages
Mesenchyme
Meta-analysis
Metastases
Natural products
Pediatrics
Phosphorylation
Proteins
Radioresistance
Software
SUMO protein
SUMO2
TCGA
Transcription
Transcriptomics
Tumors
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Summary:Abstract Background Glioblastoma multiforme (GBM) is a deadly brain tumour with minimal survival rates due to the ever-expanding heterogeneity, chemo and radioresistance. Kinases are known to crucially drive GBM pathology; however, a rationale therapeutic combination that can simultaneously inhibit multiple kinases has not yet emerged successfully. Results Here, we analyzed the GBM patient data from several publicly available repositories and deduced hub GBM kinases, most of which were identified to be SUMOylated by SUMO2/3 isoforms. Not only the hub kinases but a significant proportion of GBM upregulated genes involved in proliferation, metastasis, invasion, epithelial-mesenchymal transition, stemness, DNA repair, stromal and macrophages maintenance were also identified to be the targets of SUMO2 isoform. Correlatively, high expression of SUMO2 isoform was found to be significantly associated with poor patient survival. Conclusions Although many natural products and drugs are evidenced to target general SUMOylation, however, our meta-analysis strongly calls for the need to design SUMO2/3 or even better SUMO2 specific inhibitors and also explore the SUMO2 transcription inhibitors for universally potential, physiologically non-toxic anti-GBM drug therapy. Graphical Abstract
ISSN:1475-2867
1475-2867
DOI:10.1186/s12935-021-02279-y