Toxicity study of ochratoxin A using HEK293 and HepG2 cell lines based on microRNA profiling

Area of Science:

• Toxicology
• Molecular Biology
• Genomics

Background:

• Ochratoxin A (OTA) is a mycotoxin known to induce DNA damage, cytotoxicity, and apoptosis in mammalian cells.
• MicroRNAs (miRNAs) are crucial regulators of cellular processes and are implicated in cancer development and progression.

Purpose of the Study:

• To comparatively analyze the toxicity of OTA in human embryonic kidney (HEK293) and hepatocellular carcinoma (HepG2) cell lines using high-throughput miRNA profiling.
• To investigate the impact of OTA on miRNA biogenesis and identify deregulated pathways in vitro and in vivo.

Main Methods:

• High-throughput miRNA profiling was employed to analyze changes in miRNA expression in HEK293 and HepG2 cells treated with 25 μM OTA for 24 hours.
• Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to identify deregulated pathways.
• Comparison between in vitro cell models and in vivo models was conducted.

Main Results:

• OTA treatment led to significant alterations in miRNA expression in both cell lines, with common changes related to signal transduction pathways and distinct changes associated with human cancer pathways.
• Suppression of DGCR8, Dicer1, and Drosha in HEK293 cells indicated impaired miRNA biogenesis, with more extensive damage observed in this cell line.
• While many miRNAs differed between in vitro and in vivo models, OTA toxicity was evident in both, and the classification of deregulated pathways showed similarities.

Conclusions:

• OTA exposure deregulates miRNAs, primarily affecting signal transduction and human cancer pathways in vitro.
• MiRNA biogenesis is impaired by OTA in both cell lines studied.
• The findings highlight OTA's toxicological impact on miRNA regulation, relevant to both cellular and organismal levels.