Title: Regulation of a long noncoding RNA MALAT1 by aryl hydrocarbon receptor in pancreatic cancer cells and tissues.

Authors: Lee, Ji-Eun; Cho, Sung-Gook; Ko, Seong-Gyu; Ahrmad, Syed A; Puga, Alvaro; Kim, Kyounghyun

Published In Biochem Biophys Res Commun, (2020 11 19)

Abstract: Environmental toxicants such as dioxins and polycyclic aromatic carbons are risk factors for pancreatitis and pancreatic cancer. These toxicants activate aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, of which activation regulates many downstream biological events, including xenobiotic metabolism, inflammation, and cancer cell growth and transformation. Here, we identified that environmental toxicant-activated AHR increased expression of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in pancreatic cancer cells and pancreatic tissues. The MALAT1 is a long noncoding (lnc) RNA which interacts with Enhancer of Zeste 2 (EZH2), a histone methyltransferase with epigenetic silencer activity, and the MALAT1-EZH2 interaction increased its epigenetic silencing activity. In contrast, AHR antagonist, CH223191 or resveratrol, counteracted the AHR-mediated MALAT1 induction and MALAT1-enahnced EZH2 activity. Collectively, these results revealed a novel pathway of how environmental exposure leads to epigenetic alteration via activation of AHR-MALAT1-EZH2 signaling axis under pancreatic tissue- and cancer cell-context.

PubMed ID: 32900487

MeSH Terms: Animals; Cell Line, Tumor; Enhancer of Zeste Homolog 2 Protein/metabolism; Environmental Pollutants/toxicity; Humans; Mice, Inbred C57BL; Pancreas/drug effects; Pancreas/metabolism; Pancreatic Neoplasms/enzymology; Pancreatic Neoplasms/genetics; Pancreatic Neoplasms/metabolism*; Polychlorinated Dibenzodioxins/toxicity; RNA, Long Noncoding/biosynthesis; RNA, Long Noncoding/metabolism*; Receptors, Aryl Hydrocarbon/metabolism*; Receptors, Aryl Hydrocarbon/physiology; Signal Transduction