Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop.
The European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) organised a workshop to discuss the state-of-the-art research on noncoding RNAs (ncRNAs) as biomarkers in regulatory toxicology and as analytical and therapeutic agents. There was agreement that ncRNA expression profiling data requires careful evaluation to determine the utility of specific ncRNAs as biomarkers. To advance the use of ncRNA in regulatory toxicology, the following research priorities were identified: (1) Conduct comprehensive literature reviews to identify possibly suitable ncRNAs and areas of toxicology where ncRNA expression profiling could address prevailing scientific deficiencies. (2) Develop consensus on how to conduct ncRNA expression profiling in a toxicological context. (3) Conduct experimental projects, including, e.g., rat (90-day) oral toxicity studies, to evaluate the toxicological relevance of the expression profiles of selected ncRNAs. Thereby, physiological ncRNA expression profiles should be established, including the biological variability of healthy individuals. To substantiate the relevance of key ncRNAs for cell homeostasis or pathogenesis, molecular events should be dose-dependently linked with substance-induced apical effects. Applying a holistic approach, knowledge on ncRNAs, 'omics and epigenetics technologies should be integrated into adverse outcome pathways to improve the understanding of the functional roles of ncRNAs within a regulatory context.
Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, Leipzig University, 04107 Leipzig, Germany.
Achim
A
Aigner
BASF SE, 67056 Ludwigshafen, Germany.
Roland
R
Buesen
Centre for Radiation, Chemical and Environmental Hazards, Public Health England (PHE), Harwell Campus, Chilton, Oxfordshire, OX11 0RQ, UK.
Tim
T
Gant
Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK.
Nigel
N
Gooderham
Technical University Munich, 85354 Freising-Weihenstephan, Germany.
Helmut
H
Greim
Young Investigators Group Bioinformatics and Transcriptomics, Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research - UFZ, 04318 Leipzig, Germany.
Jörg
J
Hackermüller
European Chemicals Council (Cefic) Long-Range Research Initiative, 1160 Brussels, Belgium; Hubesch Consult BVBA, 1600 Sint-Pieters-Leeuw, Belgium.
Bruno
B
Hubesch
European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), 1160 Brussels, Belgium.
Madeleine
M
Laffont
Centre for Radiation, Chemical and Environmental Hazards, Public Health England (PHE), Harwell Campus, Chilton, Oxfordshire, OX11 0RQ, UK.
Emma
E
Marczylo
Biochemistry Centre Regensburg, University of Regensburg, 93053 Regensburg, Germany.
Gunter
G
Meister
Monsanto Company, St. Louis, MO 63167, USA.
Jay S
JS
Petrick
Dow AgroSciences, Indianapolis, IN 46268, USA.
Reza J
RJ
Rasoulpour
Scientific Consultancy - Animal Welfare, 85579 Neubiberg, Germany.
Ursula G
UG
Sauer
BioMath GmbH, 18055 Rostock, Germany.
Kerstin
K
Schmidt
Institut de Génétique Humain (IGH), Centre National de la Recherche Scientifique - National Centre of Scientific Research (CNRS), 34396 Montpellier Cedex 5, France.
Hervé
H
Seitz
Department of Pathology, Institute for RNA Medicine, Beth Israel Deaconess Medical Center - BIDMC Cancer Center Harvard Medical School, Boston, MA 02215, USA.
Frank
F
Slack
Sumitomo Chemical Europe, 1830 Machelen, Belgium.
Tokuo
T
Sukata
Neuroscience Amsterdam, VU University Medical Centre, 1081HV 1117, Amsterdam, The Netherlands.
Saskia M
SM
van der Vies
Monsanto Company, 1150 Brussels, Belgium.
Jan
J
Verhaert
The John Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kenneth W
KW
Witwer
European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), 1160 Brussels, Belgium. Electronic address: alan.poole@ecetoc.org.
Alan
A
Poole
D000818:Animals; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005819:Genetic Markers; D023281:Genomics; D006801:Humans; D023421:Models, Animal; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods*; D014116:Toxicology / Q000379:methods*
D005819:Genetic Markers; D022661:RNA, Untranslated
Adverse-outcome-pathway; Biomarker; Gene expression; Noncoding RNA (ncRNA); Phenotypic consequence; Regulatory toxicology