title: Dynamic and selective HERV RNA expression in neuroblastoma cells subjected to variation in oxygen tension and demethylation.
abstract: We studied HERV expression in cell lines after hypoxia, mitogenic stimulation, and demethylation, to better understand if hypoxia may play a role in ERV activation also within the nervous system, as represented by neuroblastoma cell lines. The level of RNA of four human ERV groups (HERVs) (HERVE, I/T, H, and W), and three housekeeping genes, of different cell lines including A549, COS-1, Namalwa, RD-L and Vero-E6, as well as human neuroblastoma cell lines SH-SY5Y, SK-N-DZ, and SK-N-AS were studied using reverse transcription and real-time quantitative PCR (QPCR). During the course of recovery from hypoxia a pronounced and selective activation of RNA expression of HERVW-like sequences, but not of HERVE, I/T, H, and three housekeeping genes, was found in the neuroblastoma cell lines, most pronounced in SK-N-DZ. In the SK-N-DZ cell line, we also tested the expression of HERVs after chemical treatments. HERVW-like sequences were selectively upregulated by 5-azacytidine, a demethylating agent. Some HERVW loci seem especially responsive to hypoxia and demethylation. HERV expression in neuroblastoma cells is selectively and profoundly influenced by some physiological and chemical stimuli.
authors.affiliation: Section of Virology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Hu
authors.affiliation: Section of Virology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Dmitrijs
authors.initials: D
authors.lastname: Uzhameckis
authors.affiliation: Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Hedborg
authors.affiliation: Section of Virology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Blomberg
mesh_terms: D001374:Azacitidine / Q000494:pharmacology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D020077:Endogenous Retroviruses / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics* / Q000821:virology*; D010100:Oxygen / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D048348:Reverse Transcription; D015854:Up-Regulation; D014775:Virus Activation / Q000187:drug effects / Q000235:genetics
chemical_list: D004791:Enzyme Inhibitors; D012367:RNA, Viral; D001374:Azacitidine; D010100:Oxygen
keywords: Co-option; Human endogenous retroviral sequences; RNA expression; demethylation; hypoxia; neuroblastoma