Caiment Florian, Gaj Stan, Claessen Sandra, Kleinjans Jos
Department of Toxicogenomics, Maastricht University, Maastricht 6200, The Netherlands
Department of Toxicogenomics, Maastricht University, Maastricht 6200, The Netherlands.
Nucleic Acids Res. 2015 Mar 11;43(5):2525-34. doi: 10.1093/nar/gkv115. Epub 2015 Feb 17.
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.
从接触有毒化合物到致癌的一系列事件仍鲜为人知。随着高通量测序技术的出现，现在有可能同时发现许多不同的生物成分。我们使用两个不同的RNA文库，对暴露于强人类致癌物苯并[a]芘的人HepG2肝细胞在六个时间点的完整转录组进行了测序。整合数据以揭示新的复杂化学-基因相互作用。值得注意的是，我们推测，苯并[a]芘诱导的miR-181a-1_3p过表达对DNA损伤反应酶MGMT的抑制作用，可能随着时间的推移导致肝癌。
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