Circulating MicroRNAs in Drug Safety Assessment for Hepatic and Cardiovascular Toxicity: The Latest Biomarker Frontier?
- PDF / 292,432 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 38 Downloads / 175 Views
CURRENT OPINION
Circulating MicroRNAs in Drug Safety Assessment for Hepatic and Cardiovascular Toxicity: The Latest Biomarker Frontier? Mitsuhiko Osaki • Nobuyoshi Kosaka Futoshi Okada • Takahiro Ochiya
•
Ó Springer International Publishing Switzerland 2013
Abstract Drug-induced liver and cardiovascular injuries are important aspects of safety evaluations of numerous drugs in development. Therefore, reliable and predictive biomarkers to allow detection of early signs of druginduced liver and cardiovascular injuries are required in clinical and preclinical pharmaceutical evaluation. MicroRNAs (miRNAs) are reported to be present in body fluids (blood, urine, etc.), and these ‘circulating miRNAs’ have been proposed as toxicological biomarkers of druginduced tissue injury in preclinical and clinical practice. To be used as biomarkers of drug toxicity, such miRNAs need to show rapid and injured-tissue–specific upregulation in body fluids after injury, be more sensitive than existing protein markers such as alanine aminotransferase (ALT) and troponins, and be able to identify the toxicants responsible, if possible. In this article, we focus on the current knowledge of circulating miRNAs, which have potential for use in assessment of drug-induced liver and cardiovascular injuries. In addition, we discuss an important question regarding normalization of the expression levels of certain circulating miRNAs in body fluids.
M. Osaki (&) F. Okada Division of Pathological Biochemistry, Department of Biomedical Sciences, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan e-mail: [email protected] M. Osaki F. Okada Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan N. Kosaka T. Ochiya Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan
1 Introduction MicroRNAs (miRNAs) are endogenous non-coding RNAs of *22 bp in length, which suppress gene expression in a sequence-specific manner and play important roles in a wide range of physiological and pathological processes [1, 2]. miRNA was first identified in Caenorhabditis elegans as RNA molecules that were complementary to the 30 untranslated regions of the target transcript, such as the lin-4 and let-7 genes [3, 4]. On the basis of miRBase release 20.0, more than 1,800 human miRNAs have been registered [5], with a large number being evolutionarily conserved [6, 7]. It has been reported that miRNAs are expressed in all animal cells and have fundamental roles in cellular activities such as development, cellular differentiation, proliferation, cell-cycle control, apoptosis, metabolism, and cancer [7]. miRNAs can downregulate gene expression by affecting mRNA stability and influencing protein synthesis in a sequence-specific manner [8]. Similarly to mRNA, some miRNAs are produced in a cell- or tissue-specific manner [9, 10]. Those specific miRNAs would be released to ouside of these cells followed
Data Loading...
