Tissue-specific response of microRNAs to carcinogenicity and mutagenicity of aristolochic acid in rats

ABSTRACT: Aristolochic acid (AA) is an active component of herbal drugs derived from the Aristolochia species that have been used for medicinal purposes since antiquity. However, AA is genotoxic and induces tumors in animals and humans. AA induces mutations and tumors in the kidney but solely mutations in the liver. To evaluate whether miRNAs could indicate AA’s tissue-specific carcinogenicity and mutagenicity, we first conducted microarray analysis of miRNA expression in kidneys and livers of rats treated with a carcinogenic dose of AA. Then, miR-21, a biomarker for carcinogenicity, and miR-34a, a biomarker for mutagenicity, the two miRNAs whose expressions were most altered, were evaluated for their expression in the kidney (the AA’s mutagenic and carcinogenic target tissue), liver (the AA’s mutagenic target tissue), and testis, the non-target tissue where neither tumors nor mutation induction was found in previous studies and in this study. Genomic analysis of miRNA expression for kidney and liver samples showed that miRNA expression was globally changed by the treatment. Nineteen miRNAs were significantly dysregulated by the treatment in the kidney. Most of these miRNAs are related to carcinogenesis. Only one miRNA, miR-34a, was differentially expressed in the liver. Expression of miR-21 was induced in the kidney by AA treatment in a dose-dependent manner while no changes occurred in the liver or testis, indicating that the kidney is the carcinogenic target. miR-34a was dose-dependently up-regulated in the kidneys and livers of rats treated with AA, but not in the testis, suggesting that the kidney and liver are mutagenic target tissues, but the testis is not. Our results demonstrate that miRNA profiles can reflect the AA’s carcinogenicity in a tissue-specific manner while specific miRNAs can signify the target tissues for carcinogenicity or mutagenicity of AA.

ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens

PROVIDER: GSE50946 | GEO | 2013/11/10

SECONDARY ACCESSION(S): PRJNA219409

REPOSITORIES: GEO