Bioinformatic Analysis Identified Hub Genes Associated with Heterocyclic Amines Induced Cytotoxicity of Peripheral Blood Mononuclear Cells

Genes (Basel). 2021 Nov 25;12(12):1888. doi: 10.3390/genes12121888.

Abstract

Heterocyclic amines (HCAs) are a set of food contaminants that may exert a cytotoxic effect on human peripheral blood mononuclear cells (PBMC). However, the genetic mechanism underlying the cytotoxicity of HCAs on PBMC has not been investigated. In the study, bioinformatic analysis on gene dataset GSE19078 was performed. The results of weighted correlation network analysis and linear models for microarray and RNA-seq data analysis showed that four gene modules were relevant to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) exposure while one gene module was correlated with 2-amino-3-methyl-3H-imidazo[4,5f]quinoline (IQ) exposure. Gene functional analysis showed that the five modules were annotated mainly with mRNA transcriptional regulation, mitochondrial function, RNA catabolic process, protein targeting, and immune function. Five genes, MIER1, NDUFA4, MLL3, CD53 and CSF3 were recognized as the feature genes for each hub gene network of the corresponding gene module, and the expression of feature genes was observed with a significant difference between the PhIP/IQ samples and the other samples. Our results provide novel genes and promising mechanisms for exploration on the genetic mechanism of HCAs on PBMC.

Keywords: IQ; PBMC; PhIP; WGCNA; hub gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / adverse effects*
  • Cells, Cultured
  • Computational Biology / methods
  • ELAV-Like Protein 2 / genetics*
  • Gene Regulatory Networks / drug effects
  • Gene Regulatory Networks / genetics
  • Humans
  • Imidazoles / adverse effects
  • Leukocytes, Mononuclear / drug effects
  • Mutagens / adverse effects
  • Pyridines / adverse effects
  • Quinolines / adverse effects
  • RNA, Messenger / genetics
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics

Substances

  • Amines
  • ELAV-Like Protein 2
  • ELAVL2 protein, human
  • Imidazoles
  • Mutagens
  • Pyridines
  • Quinolines
  • RNA, Messenger
  • 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
  • quinoline
  • pyridine