The mammalian genome is transcribed into mRNAs that code for protein as well as a broad spectrum of other noncoding (nc) RNA products. Long ncRNAs (lncRNA), defined as ncRNA species > 200 nucleotides long, are emerging as important epigenetic regulators of gene expression that are involved in a spectrum of biological processes of relevance to toxicology.
A team led by researchers at ILS Genomics conducted a gene expression profiling study in the livers of female B6C3F1 mice exposed to the carcinogen furan at 0.0, 1.0, 2.0, (non-carcinogenic doses) and at 4.0, 8.0 mg/kg (carcinogenic doses) for 3 weeks. LncRNA differential expression showed a non-linear dose response with none differentially expressed at 1.0 or 2.0 mg/kg, two lncRNAs at 4.0 mg/kg furan, and 83 at 8 mg/kg, representing 13.3% (83/632) of the total number of differentially expressed transcripts. Among the lncRNAs observed, -two lncRNAs examined showed transcriptional clustering with nearby protein coding genes. LncRNA-p21, is anl anti-sense transcript that is 15 kb downstream from Cdkn1a locus and appears to be co-transcribed with the protein coding gene Cdkn1a at 8.0 mg/kg furan. In a separate independent study, RNA samples from the livers of mice administered benzo(a)pyrene also demonstrated increase levels of Cdkn1a and the antisense lncRNA-p21 transcript. These data demonstrate that lncRNAs are transcriptional targets of furan-exposures associated with levels of furan that are cytotoxic, and induce cell proliferation. In addition, certain lncRNA transcripts are associated with the expression of nearby coding protein genes. The researchers hypothesize that lncRNAs have potential as epigenetic biomarkers of carcinogenic exposures.
- Recio L, Phillips SL, Maynor T, Waters M, Jackson AF, Yauk CL. (2013) Differential Expression of Long Non-Coding RNAs in the Livers of Female B6C3F1 Mice Exposed to the Carcinogen Furan. Toxicol Sci [Epub ahead of print]. [abstract]