The role for microRNAs in drug toxicity and in safety assessment.
BACKGROUND
Adverse drug reactions present significant challenges that impact pharmaceutical development and are major burdens to public health services worldwide. In response to this need, the field of toxicology is rapidly expanding to identify key pathways involved in drug toxicity.


METHODS
MicroRNAs (miRNAs) are a class of small evolutionary conserved endogenous non-coding RNAs that regulate the translation of protein-coding genes. A wide range of toxicants alter miRNA levels in target organs and these altered miRNAs can also be detected in easily accessible biological fluids. This, combined with an early miRNA response to toxic insults and miRNA stability, substantiates the potential for these small molecules to be useful biomarkers for drug safety assessment.


CONCLUSIONS
miRNAs are early indicators and useful tools to detect drug-induced toxicity. Incorporation of miRNA profiling into the drug safety testing process will complement currently used techniques and may substantially enhance drug safety. With the increasing interests in translational research, the field of miRNA biomarker research will continue to expand and become an important part of the investigation of human drug toxicity.
FDA-National Center for Toxicological Research, Division of Biochemical Toxicology , Jefferson, AR , USA igor.pogribny@fda.hhs.gov.
April K
AK
Marrone
Frederick A
FA
Beland
Igor P
IP
Pogribny
D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D011634:Public Health; D018570:Risk Assessment / Q000379:methods; D018675:Toxicity Tests / Q000379:methods; D057170:Translational Research, Biomedical / Q000639:trends
D015415:Biomarkers; D035683:MicroRNAs
adverse drug reactions; drug toxicity; microRNAs; safety assessment