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.
Tamarixetin, a flavonoid derived from Quercetin, was shown to possess anti-cancer properties in various types of cancer. However, the mechanism of action of this compound is not well understood. Observations from reverse docking and network pharmacology analysis, were validated by cell based studies to analyse the chemotherapeutic potential and elucidate the molecular mechanism of action of Tamarixetin in breast cancer. In silico analysis using reverse docking and PPI analysis clearly indicated that out of 35 proteins targeted by Tamarixetin, the top 3 hub genes, namely, AKT1, ESR1 and HSP90AA1, were upregulated in breast tumor tissues and more importantly showed strong negative correlation to breast cancer patient survival. Furthermore, the KEGG pathway analysis showed enrichment of target proteins of Tamarixetin in 33 pathways which are mainly involved in neoplastic signalling. In vitro cell-based studies demonstrated that Tamarixetin could inhibit cell proliferation, induce ROS and reduce mitochondrial membrane potential, leading to cell death. Tamarixetin induced cell cycle arrest at G2/M phase and inhibited the migration as well as the invasion of breast cancer cells. Taken together, the combination of in silico and in vitro approaches used in the present study clearly provides evidence for the chemotherapeutic potential of Tamarixetin in breast cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.