ABSTRACT
BACKGROUND: microRNA expression profile analysis provides evaluation of the early stages of carcinogenesis. This study focuses on early alteration of miRNA expression after treatment with different carcinogens. MATERIALS AND METHODS: Mice were intraperitoneally injected with one dose of 7,12-dimethylbenz(α)anthracene (DMBA) and N-methyl-N-nitrosourea (MNU). The expression of miRNAs were analyzed 3 and 6 hours after the treatment, using quantitative real-time-polymerase chain reaction. RESULTS: Underexpression of miR-34a and miR-155 were detected in the liver, spleen and kidneys at 3 and 6 hours after MNU treatment. In the lungs and kidneys, the expression of miR-21 was significantly elevated 6 hours after DMBA treatment, while in the liver, MNU induced higher expression levels of miR-21 at 3 and 6 hours compared to treatment with DMBA. CONCLUSION: The different response of miRNAs to carcinogens emphasizes their possible role as potential epidemiological biomarkers in early phases of environmental tumorigenesis.
Subject(s)
9,10-Dimethyl-1,2-benzanthracene/toxicity , Gene Expression Regulation/drug effects , Methylnitrosourea/toxicity , MicroRNAs/genetics , Alkylating Agents/toxicity , Animals , Carcinogens/toxicity , Female , Gene Expression Profiling , Kidney/drug effects , Kidney/metabolism , Liver/drug effects , Liver/metabolism , Lung/drug effects , Lung/metabolism , Mice , Mice, Inbred CBA , Reverse Transcriptase Polymerase Chain Reaction , Spleen/drug effects , Spleen/metabolism , Time FactorsABSTRACT
BACKGROUND: 7,12-Dimethylbenz(α)anthracene (DMBA) is a carcinogen capable of inducing various types of tumors. MATERIALS AND METHODS: We investigated the effect of DMBA on micro-RNA expression in CBA/CA H2(k) inbred mice after 24 hours and one week from exposure. RESULTS: Expression levels of miR-21, miR-146a and let-7a were significantly higher in the vital organs of the mice 24 hours after DMBA exposure compared to those of the controls. On the other hand, a significant down-regulation of the miRNAs was observed seven days after DMBA administration. CONCLUSION: Based on our data, DMBA has an impact on the expression of miR-21, let-7a and miR-146a genes. The altered micro-RNA expression can be regarded as an early effect of exposure to chemical carcinogens. To our knowledge, this is the first study of miRNA modulation caused by DMBA in non-malignant tissues.
Subject(s)
9,10-Dimethyl-1,2-benzanthracene/toxicity , Gene Expression Regulation/drug effects , MicroRNAs/genetics , Animals , Carcinogens/toxicity , Female , Gene Expression Profiling , Kidney/drug effects , Kidney/metabolism , Lung/drug effects , Lung/metabolism , Male , Mice , Mice, Inbred CBA , Reverse Transcriptase Polymerase Chain Reaction , Spleen/drug effects , Spleen/metabolism , Time FactorsABSTRACT
Cancer research concerning short non-coding RNA sequences and functionally linked to RNA interference (RNAi) have reached explosive breakthrough in the past decade. Molecular technology applies microRNA in extremely wide spectrum from molecular tumor prediction, diagnostics, progression monitoring and prevention. Functional analysis of tissue miRNA and cell-free serum miRNA in posttranscription and translation regulation innovated and restructured the knowledge on the field. This review focuses on molecular epidemiology and primary prevention aspects of the small non-coding RNA sequences.
Subject(s)
Biomarkers, Tumor/blood , MicroRNAs/metabolism , Neoplasms/genetics , RNA Interference , RNA, Small Untranslated/metabolism , Biomarkers/metabolism , Gene Expression Regulation , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/biosynthesis , MicroRNAs/blood , Molecular Epidemiology , Neoplasms/prevention & control , Predictive Value of TestsABSTRACT
BACKGROUND: Genetic polymorphisms of metabolizing enzymes may affect the risk of cancer formation in humans. Since the diet can contain polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HAs), the relationship between polymorphisms of enzymes involved in PAH and HA metabolism and the occurrence of sporadic colorectal cancer was studied. PATIENTS AND METHODS: Five hundred colorectal cancer patients and 500 controls were genotyped for cytochrome P450 enzymes (CYP) 1A1 Ile/Val, CYP 1A2*1F, CYP 2E1 c1/c2, microsomal epoxy hydrolase (mEH) exon 3 Tyr113His and exon 4 His139Arg polymorphisms by allele-specific polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism (RFLP). RESULTS: The presence of CYP 1A1 Val, CYP 2E1 c2 and mEH exon 3 His alleles was statistically significantly associated with the occurrence of colorectal cancer (OR: 1.44 95% CI: 1.04-2.00; OR: 1.74 95% CI: 1.15-2.65; OR: 1.79 95% CI: 1.10-2.92, respectively). CONCLUSION: These findings suggest that allelic polymorphism of metabolizing enzymes play an important role in human colorectal carcinogenesis by affecting the metabolism of dietary carcinogens.
