Combining mendelian randomization analysis and network toxicology strategy to identify causality and underlying mechanisms of environmental pollutants with glioblastoma: A study of Methyl-4-hydroxybenzoate.

Background: An increasing number of environmental pollutants are associated with human diseases. We explored the mechanisms by which an aromatic small molecule -- Methyl-4-hydroxybenzoate (MEP) contribute to the development of glioblastoma (GBM).

Methods: The causality of MEP and GBM were identified via the Mendelian Randomization (MR) analysis. We identified the key targets by integrating the targets of GBM, differential expressed genes (DEGs) from GEO and target genes of MEP. The network of hub genes was obtained from STRING and Cytoscape tools and GO, KEGG enrichment analysis were conducted by clusterProfiler R package. These hub targets were executed molecular docking via Autodock software.

Results: MEP had a causal association with GBM as risk factors (P < 0.05, OR > 1). 46 key targets were derived, in which CASP3, MMP2 and CDK4 were screened as the hub targets. MEP might play a role in the GBM by affecting the pathways of neuroactive ligand-receptor interaction, Molecular docking analysis showed a good binding ability of between MEP and CASP3, MMP2, CDK4, CASP8 and MCL1.

Conclusions: A causal relationship between MEP and GBM exists. CASP3, MMP2, CDK4, CASP8 and MCL1 have been identified as the crucial targets correlating with GBM. This discovery may provide an important insight into how environmental pollutants contribute to the development of GBM.