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Whole genome analysis and microRNAs regulation in HepG2 cells exposed to cadmium
Marco Fabbri1, Chiara Urani, Maria Grazia Sacco
1Institute for Health and Consumer Protection, Molecular Biology and Genomics Unit, Joint Research Centre, Ispra (VA), Italy. marco.fabbri@jrc.ec.europa.eu
Abstract:
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 μM and 10 μM Cd using an Agilent microarray. Furthermore, we evaluated the microRNA modulation after exposure to 10 μM 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.
Insights
Cadmium exposure alters gene and microRNA expression in liver cells, potentially impacting cancer pathways and liver function. This study reveals cadmium
Area of Science:
- Toxicology
- Molecular Biology
- Genomics
Background:
- Cadmium (Cd) is a toxic and carcinogenic metal.
- Its precise mechanisms of action require further elucidation.
- Understanding Cd's effects on cellular processes is crucial.
Purpose of the Study:
- To investigate gene expression modulation in HepG2 cells exposed to Cadmium.
- To evaluate microRNA modulation following Cadmium exposure.
- To elucidate Cadmium's impact on cancer-related and liver function pathways.
Main Methods:
- Human hepatoma HepG2 cells were exposed to 2 μM and 10 μM Cadmium.
- Agilent microarray was used for gene expression profiling.
- Low Density Array was employed for microRNA profiling.
Main Results:
- Low Cadmium concentration (2 μM) regulated metallothionein family genes.
- High Cadmium concentration (10 μM) led to significant gene expression changes, with up-regulated genes linked to cancer pathways and down-regulated genes to liver function.
- Several microRNAs, notably from the let-7 family (oncosuppressors), were modulated.
Conclusions:
- Cadmium exposure significantly alters gene and microRNA expression in HepG2 cells.
- The observed changes suggest Cadmium's potential role in cancer development and liver dysfunction.
- MicroRNAs may play a role in Cadmium-induced regulatory pathways.
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