Identification of microRNAs regulated by isothiocyanates and association of polymorphisms inside their target sites with risk of sporadic colorectal cancer
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- 3' Untranslated Regions MeSH
- Cell Line drug effects MeSH
- DEAD-box RNA Helicases genetics MeSH
- Epithelial Cells drug effects pathology MeSH
- Genetic Predisposition to Disease MeSH
- Homozygote MeSH
- Isothiocyanates pharmacology MeSH
- Polymorphism, Single Nucleotide * MeSH
- Colorectal Neoplasms genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs genetics MeSH
- Protective Agents pharmacology MeSH
- Computer Simulation MeSH
- Gene Expression Regulation drug effects MeSH
- Ribonuclease III genetics MeSH
- Aged MeSH
- Gene Expression Profiling MeSH
- Case-Control Studies MeSH
- Sulfoxides MeSH
- Binding Sites genetics MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 3' Untranslated Regions MeSH
- DEAD-box RNA Helicases MeSH
- DICER1 protein, human MeSH Browser
- iberin MeSH Browser
- Isothiocyanates MeSH
- MicroRNAs MeSH
- MIRN155 microRNA, human MeSH Browser
- MIRN23a microRNA, human MeSH Browser
- MIRN27 microRNA, human MeSH Browser
- Protective Agents MeSH
- Ribonuclease III MeSH
- sulforaphane MeSH Browser
- Sulfoxides MeSH
Sporadic colorectal cancer (CRC) is a typical multifactorial disease. Isothiocyanates (ITC) have been recently shown to inhibit development of CRC in many experimental models. MicroRNAs (miRNAs) are short noncoding RNAs that posttranscriptionally regulate gene expression through binding to 3' untranslated regions (3'UTR) of target mRNAs. MiRNAs are regulated by natural agents, ITCs included. In our study, using global expression profiling based on TaqMan Low-Density Arrays, we identified 3 common miRNAs (miR-155, miR-23b, miR-27b) regulated by ITCs (sulforaphane, iberin) in colonic epithelial cell lines NCM460 and NCM356. In silico predictions allowed us to find 9 relevant single nucleotide polymorphisms (SNPs) localized within the 3'UTRs of genes (AGTR1, TNFAIP2, PRKCB, HSPA9, RABGAP1, DICER1, ADAM19, VWA5A, and SIRT5) targeted by these ITC-related miRNAs. Finally, we observed that homozygous CC genotype of DICER1, rs1057035, was significantly associated with decreased risk of CRC (odds ratio = 0.49; 95% confidence interval: 0.25-0.95, P = 0.036) when compared to TT homozygote genotype; also, the C allele tended to have a protective effect (P = 0.072). This study showed that miRNAs could be involved in chemoprotective effects of natural agents; their function alteration through SNPs in their binding sites and flanking regions presents a new class of CRC risk factors.
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