Analysis of microarray data for identification of key microRNA signatures in glioblastoma multiforme

Abstract

Glioblastoma multiforme (GBM) is one of the most malignant types of glioma known for its reduced survival rate and rapid relapse. Previous studies have shown that the expression patterns of different microRNAs (miRNA/miR) play a crucial role in the development and progression of GBM. In order to identify potential miRNA signatures of GBM for prognostic and therapeutic purposes, we downloaded and analyzed two expression data sets from Gene Expression Omnibus profiling miRNA patterns of GBM compared with normal brain tissues. Validated targets of the deregulated miRNAs were identified using MirTarBase, and were mapped to Search Tool for the Retrieval of Interacting Genes/Proteins, Database for Annotation, Visualization and Integrated Discovery and Kyoto Encyclopedia of Genes and Genomes databases in order to construct interaction networks and identify enriched pathways of target genes. A total of 6 miRNAs were found to be deregulated in both expression datasets studied. Pathway analysis demonstrated that most of the target genes were enriched in signaling cascades connected to cancer development, such as ‘Pathways in cancer’, ‘Focal adhesion’ and ‘PI3K-Akt signaling pathway’. Of the five target genes that were enriched in the glioblastoma pathway, in the WikiPathway database, both HRas proto-oncogene, GTPase and MET proto-oncogene, receptor tyrosine kinase target genes of hsa-miR-139-5p, were found to be significantly associated with patient survival. The present study may thus form the basis for further exploration of hsa-miR-139-5p, not only as a therapeutic agent, but also as a diagnostic biomarker for GBM as well as a predictive marker for patient survival.

System analysis based on the ER stress-related genes identifies WFS1 as a novel therapy target for colon cancer

“…Consistent with previous studies, BCL2 is upregulated in breast, prostate, colorectal, lung, stomach, ovarian cancer, and other solid tumors [ 28 ]. The inhibition of BCL2 expression by hsa-miR-139-5p in colorectal cancer cells increased chemosensitivity [ 29 ]. Chuyong Lin et al confirmed that FLOT1 promotes breast cancer cell proliferation and tumorigenesis [ 30 ].…”

Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma

“…PELP1 is co-regulator of several nuclear receptors, and a potent activator of β-catenin and Wnt signaling [ 115 ]. MicroRNA and lncRNA profiling of GBM versus the normal brain revealed the role of epigenetic mechanisms in the activation of Wnt signaling in GBM [ 116 , 117 ].…”

The Importance of Tumor Stem Cells in Glioblastoma Resistance to Therapy

“…They also reported that mesenchymal transformation was triggered by Wnt/β-catenin signaling activation, confirming the importance of this targeting to overcome pharmaco-resistance in GBM. Lastly, a new study pointed to the role of epigenetic modifications in the regulation of the Wnt pathway assuming that the different patterns of microRNAs (miRNA/miR), such as miR-138-2-3p and miR-770-5p, may carry out a key role in the development and progression of GBM [ 99 ].…”