title: High-throughput data integration of RNA-miRNA-circRNA reveals novel insights into mechanisms of benzo[a]pyrene-induced carcinogenicity.
abstract: The chain of events leading from a toxic compound exposure to carcinogenicity is still barely understood. With the emergence of high-throughput sequencing, it is now possible to discover many different biological components simultaneously. Using two different RNA libraries, we sequenced the complete transcriptome of human HepG2 liver cells exposed to benzo[a]pyrene, a potent human carcinogen, across six time points. Data were integrated in order to reveal novel complex chemical-gene interactions. Notably, we hypothesized that the inhibition of MGMT, a DNA damage response enzyme, by the over-expressed miR-181a-1_3p induced by BaP, may lead to liver cancer over time.
authors.affiliation: Department of Toxicogenomics, Maastricht University, Maastricht 6200, The Netherlands florian.caiment@maastrichtuniversity.nl.
authors.forename: Florian
authors.initials: F
authors.lastname: Caiment
authors.affiliation: Department of Toxicogenomics, Maastricht University, Maastricht 6200, The Netherlands.
authors.forename: Stan
authors.initials: S
authors.lastname: Gaj
authors.affiliation: Department of Toxicogenomics, Maastricht University, Maastricht 6200, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: Claessen
authors.affiliation: Department of Toxicogenomics, Maastricht University, Maastricht 6200, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Kleinjans
mesh_terms: D001564:Benzo(a)pyrene / Q000494:pharmacology*; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics*; D059467:Transcriptome / Q000187:drug effects* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D001564:Benzo(a)pyrene; D012313:RNA; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes