Abstract

Glioblastoma (GBM) is the most common malignant brain tumor and its malignant phenotypic characteristics are classified as grade IV tumors. Molecular interactions, such as protein–protein, protein–ncRNA, and protein–peptide interactions are crucial to transfer the signaling communications in cellular signaling pathways. Evidences suggest that signaling pathways of stem cells are also activated, which helps the propagation of GBM. Hence, it is important to identify a common signaling pathway that could be visible from multiple GBM gene expression data. microRNA signaling is considered important in GBM signaling, which needs further validation. We performed a high-throughput analysis using micro array expression profiles from 574 samples to explore the role of non-coding RNAs in the disease progression and unique signaling communication in GBM. A series of computational methods involving miRNA expression, gene ontology (GO) based gene enrichment, pathway mapping, and annotation from metabolic pathways databases, and network analysis were used for the analysis. Our study revealed the physiological roles of many known and novel miRNAs in cancer signaling, especially concerning signaling in cancer progression and proliferation. Overall, the results revealed a strong connection with stress induced senescence, significant miRNA targets for cell cycle arrest, and many common signaling pathways to GBM in the network.

Highlights

  • Glioblastoma (GBM) is the most common aggressive brain tumor, rendering it incurable by surgery [1,2,3,4]

  • Several molecular signaling pathways urge the abnormal growth of cells, such as epidermal growth factor (EGF), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), and hepatocyte growth factor/scatter factor (HGF/SF) [5]

  • We identified novel senescence-related pathways involved in GBM through micro array expression data

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Summary

Introduction

Glioblastoma (GBM) is the most common aggressive brain tumor, rendering it incurable by surgery [1,2,3,4]. It is significant to reveal the interactions of the significant proteins, protein–ncRNA, and protein–peptide to target the crucial signaling pathway in GBM. MicroRNA signaling communication tends to have an important role in GBM signaling, which needs further validation and understanding [6,7]. Small non-coding RNA and microRNA (miRNA) signaling tend to have an essential role in GBM signaling, requiring further validation and understanding [6,7]. GBM patient miRNA microarray data analysis identified 752 miRNAs, in which 115 miRNAs were upregulated and 24 miRNAs were downregulated. It is identified that the toll-like receptors (TLR) in cancer stem cells interact with mRNA in the central nervous system to influence TLR-4 signaling pathway [11,12]

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