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MicroRNAs and Their Predicted TargetMessenger RNAs are Deregulated by Exposure to a Carcinogenic Dose of Comfrey in Rat Liver

ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs that function as regulators of gene expression to control cell growth and differentiation. MiRNA levels are substantially altered in various types of tumors and have been used as biomarkers in defining malignant status. However, studies on responses of miRNA expression to carcinogen insults in their target tissues are rare. In this study, we analyzed miRNA expression in the livers of rats treated with carcinogenic dose of comfrey (Symphytum officinale), a rat botanical carcinogen.

ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens

PROVIDER: GSE22655 | GEO | 2010/12/01

SECONDARY ACCESSION(S): PRJNA128023

REPOSITORIES: GEO

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Project description:MicroRNAs (miRNAs) play an important role in carcinogenesis by regulating the protein translation from their targeted messenger RNAs (mRNA). Aristolochic Acid (AA) is a potent carcinogen that can induce kidney tumors in both human and experimental animals. Although the expression and roles of miRNAs have been extensively studied in cancer tissues or tissues treated by carcinogens, it is still unclear how the three levels of gene expression, including miRNA, mRNA and protein, are regulated and coordinated during the early stage of carcinogenesis. Here, we treated rats with 10 mg/kg AA or vehicle control for 12 weeks and the kidney tissues were quickly isolated and frozen immediately after the treatment. Eight kidney samples (4 for the treatment and 4 for the control) were used for analyzing miRNA and mRNA expressions with deep sequencing, and protein expressions with proteomics. MiRNA expressions were significantly changed by AA treatment. The treated samples were well separated from the control samples in both principal component analysis (PCA) and hierarchical clustering analysis (HCA). Quantitative measurements of six miRNAs using TaqMan real-time PCR were consistent with the deep sequencing results in terms of both direction and magnitude of gene expression change. Sixty-three miRNAs (adjusted p value < 0.05 and fold change > 1.5), 6,794 mRNAs (adjusted p value < 0.05 and fold change > 2.0), and 800 proteins (fold change > 2.0) were significantly altered by AA treatment. By combining the results of a computational target predicting algorithm, and the mRNA and protein expression data, 143 genes were found by the differentially expressed miRNAs (DEMs). The DEM-targeted genes are mainly related to cancer, cell growth, which reflects the carcinogenic processes in the AA-treated rat kidneys. Groups of four 6 week-old male Big Blue rats were treated with AA as its sodium salt at 10.0 mg/kg body weight by gavage (4 ml/kg body weight) 5 times a week for 12 weeks. The rats that were treated with 0.9% sodium chloride on the same schedule were used as control. microRNAs were isolated from rat kidneys and subject to next-generation sequencing to determine the expression profile.

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MicroRNAs and Their Predicted TargetMessenger RNAs are Deregulated by Exposure to a Carcinogenic Dose of Comfrey in Rat Liver

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