4.6 Article

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

Journal

GENES
Volume 12, Issue 12, Pages -

Publisher

MDPI
DOI: 10.3390/genes12121888

Keywords

PhIP; IQ; PBMC; WGCNA; hub gene

Funding

  1. National Key R&D Program of China [2017 YFC1600402]

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The study identified five gene modules related to HCAs exposure in PBMC, with functions in mRNA transcriptional regulation, mitochondrial function, RNA catabolic process, protein targeting, and immune function. Additionally, specific genes MIER1, NDUFA4, MLL3, CD53, and CSF3 were recognized as feature genes in these modules. The expression of these feature genes showed significant differences between PhIP/IQ exposed samples and other samples.
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.

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