%0 Journal Article
%T Teratogen-induced alterations in microRNA-34, microRNA-125b and microRNA-155 expression: correlation with embryonic p53 genotype and limb phenotype
%A Keren Gueta
%A Natali Molotski
%A Natalie Gerchikov
%A Eyal Mor
%A Shoshana Savion
%A Amos Fein
%A Vladimir Toder
%A Noam Shomron
%A Arkady Torchinsky
%J BMC Developmental Biology
%D 2010
%I BioMed Central
%R 10.1186/1471-213x-10-20
%X The limbs of p53 positive embryos were more sensitive to CP-induced teratogenic insult than the limbs of p53 negative embryos. The hindlimbs were more severely affected than the forelimbs. Robust miRNA-34a expression was observed in the fore- and hindlimbs of p53+/+ embryos exposed to 12.5 mg/kg CP. The dose of 20 mg/kg CP induced almost a two-fold increase in the level of miRNA-34a expression as compared to that exhibited by p53+/+ embryos exposed to a lower dose. Increased miRNA-34b and miRNA-34c expression was also observed. Of note, this dose activated miRNA-34a and miRNA-34c in the forelimbs of p53-/- embryos. When embryos were exposed to 40 mg/kg CP, the expression pattern of the miRNA-34a/b/c was identical to that registered in the limbs of embryos exposed to 20 mg/kg CP. However, this dose suppressed miRNA-125b and miRNA-155 expression in the fore- and hindlimbs of p53+/+ embryos.This study demonstrates that teratogen-induced limb dysmorphogenesis may be associated with alterations in miRNA-34, miRNA-125b and miRNA-155 expression. It also suggests for the first time that p53-independent mechanisms exist contributing to teratogen-induced activation of miRNA-34a and miRNA-34c. At the same time, teratogen-induced suppression of miRNA-125b and miRNA-155 expression may be p53 dependent. The analysis of correlations between the expression pattern of the tested miRNAs and CP induced limb phenotypes implies that miRNAs regulating apoptosis may differ from each other with respect to their functional role in teratogenesis: some miRNAs act to protect embryos, whereas other miRNAs boost a teratogen-induced process of maldevelopment to induce embryonic death.Mature microRNAs (miRNAs) are non-coding RNAs composed of about 22-nucleotide, that attenuate gene activity posttranscriptionally by inhibiting effective mRNA translation of target genes. Silencing takes place through sequence-specific base pairing between the miR and its target mRNAs [1,2]. By now, hundreds of miRNA
%U http://www.biomedcentral.com/1471-213X/10/20