4.2 Article

Whole genome analysis and microRNAs regulation in HepG2 cells exposed to cadmium

Journal

ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
Volume 29, Issue 2, Pages 173-182

Publisher

SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH
DOI: 10.14573/altex.2012.2.173

Keywords

cadmium; gene ontology; HepG2 cells; pathway mapping; toxicogenomics

Funding

  1. Fondo di Ateneo per la Ricerca
  2. Universita di Milano Bicocca
  3. European Commission

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Cadmium (Cd) is a metal known to be toxic and carcinogenic, but its mechanism of action remains to be fully elucidated. We investigated the gene expression modulation in the human hepatoma cell line HepG2 after exposure to 2 mu M and 10 mu M Cd using an Agilent microarray. Furthermore, we evaluated the microRNA modulation after exposure to 10 mu M Cd with a Low Density Array. At the low concentration only eleven genes belonging to the metallothionein familiy were regulated. At the higher concentration the pathway enrichment analysis for the 536 up-regulated genes showed a large number of pathways related to cancer, whereas the 424 down-regulated genes were enriched on pathways correlated to liver function. A large percentage of modified microRNAs belonged to the let-7 family, which is considered to have oncosuppressor functions. Several pathways connected to cancer were regulated at the transcription level, and miRNAs had a potential impact on the modulation of this regulation.

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