In silico analysis identified miRNA‑based therapeutic agents against glioblastoma multiforme

Oncol Rep. 2019 Apr;41(4):2194-2208. doi: 10.3892/or.2019.7022. Epub 2019 Feb 19.

Abstract

MicroRNAs (miRNAs or miRs) contribute to the development of various malignant neoplasms, including glioblastoma multiforme (GBM). The present study aimed to explore the pathogenesis of GBM and to identify latent therapeutic agents for patients with GBM, based on an in silico analysis. Gene chips that provide miRNA expression profiling in GBM were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEMs) were also determined via the RobustRankAggreg algorithm. The target genes of DEMs were predicted and then intersected with GBM‑associated genes that were collected from the Gene Expression Profiling Interactive Analysis. Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the overlapping genes were then performed. Simultaneously, a connectivity map (CMap) analysis was performed to screen for potential therapeutic agents for GBM. A total of 10 DEMs (hsa‑miR‑196a, hsa‑miR‑10b, hsa‑miR‑196b, hsa‑miR‑18b, hsa‑miR‑542‑3p, hsa‑miR‑129‑3p, hsa‑miR‑1224‑5p, hsa‑miR‑876‑3p and hsa‑miR‑770‑5p) were obtained from three GEO gene chips (GSE25631, GSE42657 and GSE61710). Then, 1,720 target genes of the 10 miRNAs and 4,185 differently expressed genes in GBM were collected. By intersecting the aforementioned gene clusters, the present study identified 390 overlapping genes. GO and KEGG analyses of the 390 genes demonstrated that these genes were involved in certain cancer‑associated biological functions and pathways. Eight genes [(GTPase NRas (NRAS), calcium/calmodulin‑dependent protein kinase type II subunit Gamma (CAMK2G), platelet‑derived growth factor receptor alpha (PDGFRA), calmodulin 3 (CALM3), cyclin‑dependent kinase 6 (CDK6), calcium/calmodulin‑dependent protein kinase type II subunit beta (CAMK2B), retinoblastoma‑associated protein (RB1) and protein kinase C beta type (PRKCB)] that were centralized in the glioma pathway were selected for CMap analysis. Three chemicals (W‑13, gefitinib and exemestane) were identified as putative therapeutic agents for GBM. In summary, the present study identified three miRNA‑based chemicals for use as a therapy for GBM. However, more experimental data are needed to verify the therapeutic properties of these latent drugs in GBM.

MeSH terms

  • Androstadienes / chemistry
  • Androstadienes / pharmacology
  • Androstadienes / therapeutic use
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Computational Biology
  • Drug Discovery / methods*
  • Gefitinib / chemistry
  • Gefitinib / pharmacology
  • Gefitinib / therapeutic use
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks / drug effects
  • Gene Regulatory Networks / genetics
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Humans
  • MicroRNAs / metabolism*
  • Molecular Docking Simulation
  • Molecular Targeted Therapy / methods
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use
  • Transcriptome / genetics

Substances

  • Androstadienes
  • Antineoplastic Agents
  • MicroRNAs
  • Sulfonamides
  • N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide
  • exemestane
  • Gefitinib