nach oben

Molecular Diagnosis & Therapy

Erschienen in:

01.04.2014 | Current Opinion

Circulating MicroRNAs in Drug Safety Assessment for Hepatic and Cardiovascular Toxicity: The Latest Biomarker Frontier?

verfasst von: Mitsuhiko Osaki, Nobuyoshi Kosaka, Futoshi Okada, Takahiro Ochiya

Erschienen in: Molecular Diagnosis & Therapy | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

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 drug-induced 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 drug-induced 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.

Bartel DP. MicroRNAs: genomics biogenesis, mechanism, and function. Cell. 2004;116:281–97.PubMedCrossRef

Stefani G, Slack FJ. Small noncoding RNAs in animal development. Nat Rev Mol Cell Biol. 2008;9:219–30.PubMedCrossRef

Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.PubMedCrossRef

Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in C. elegans. Science. 2001;294:858–62.PubMedCrossRef

http://www.mirbase.org/. Accessed Jun 2013.

Bentwich I, Avniel A, Karov Y, et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet. 2005;37:766–70.PubMedCrossRef

Lagos-Quintana M, Rauhut R, Meyer J, et al. New microRNAs from mouse and human. RNA. 2003;9:175–9.PubMedCentralPubMedCrossRef

Shah AA, Leidinger P, Blin N, et al. miRNA: small molecules as potential novel biomarkers in cancer. Curr Med Chem. 2010;17:4427–32.PubMedCrossRef

Wang K, Zhang S, Marzolf B, et al. Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci USA. 2009;106:4402–7.PubMedCentralPubMedCrossRef

10.

Weber JA, Baxter DH, Zhang S, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56:1733–41.PubMedCrossRef

11.

Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;10:997–1006.CrossRef

12.

Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;101:2087–92.PubMedCrossRef

13.

Kosaka N, Ochiya T. Unraveling the mystery of cancer by secretory microRNA: horizontal microRNA transfer between living cells. Front Genet. 2011;2:97.PubMedCentralPubMed

14.

Turchinovich A, Weiz L, Langheinz A, et al. Characterization of extracellular circulating microRNA. Nucleic Acid Res. 2011;39:7223–33.PubMedCentralPubMedCrossRef

15.

Chim SS, Shing TK, Hung EC, et al. Detection and characterization of placental microRNAs in maternal plasma. Clin Chem. 2008;54:482–90.PubMedCrossRef

16.

Lawrie CH, Gal S, Dunlop HM, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141:672–5.PubMedCrossRef

17.

Vickers KC, Palmisano BT, Shoucri BM, et al. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol. 2011;13:423–33.PubMedCentralPubMedCrossRef

18.

Arroyo JD, Chevillet JR, Kroh EM, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA. 2011;108:5003–8.PubMedCentralPubMedCrossRef

19.

Ghosh AK, Secreto CR, Knox TR, et al. Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression. Blood. 2010;115:1755–64.PubMedCentralPubMedCrossRef

20.

Lima LG, Chammas R, Monteiro RQ, et al. Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent manner. Cancer Lett. 2009;283:168–75.PubMedCrossRef

21.

Skog J, Wurdinger T, Van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10:1470–6.PubMedCentralPubMedCrossRef

22.

Wolfers J, Lozier A, Raposo G, et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med. 2001;7:297–303.PubMedCrossRef

23.

Holmgren L, Szeles A, Rajnavolgyi E, et al. Horizontal transfer of DNA by the uptake of apoptotic bodies. Blood. 1999;93:3956–63.PubMed

24.

Zernecke A, Bidzhekov K, Noels H, et al. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal. 2009;2:ra81.PubMed

25.

Gilad S, Meiri E, Yogev Y, et al. Serum microRNAs are promising novel biomarkers. PLoS One. 2008;3:e3148.PubMedCentralPubMedCrossRef

26.

Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Nat Acad Sci USA. 2008;105:10513–8.PubMedCentralPubMedCrossRef

27.

Brase JC, Wutting D, Kuner R, et al. Serum microRNAs as non-invasive biomarkers for cancer. Mol Cancer. 2010;9:306.PubMedCentralPubMedCrossRef

28.

Wang JF, Yu ML, Yu G, et al. Serum miR-146a and miR-223 as potential new biomarkers for sepsis. Biochem Biophys Res Commun. 2010;394:184–8.PubMedCrossRef

29.

Moussay E, Wang K, Cho JH, et al. MicroRNA as biomarkers and regulators in B-cell chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2011;108:6573–8.PubMedCentralPubMedCrossRef

30.

Hu Z, Chen X, Zhao Y, et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol. 2010;28:1721–6.PubMedCrossRef

31.

Ng EK, Chong WW, Jin H, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut. 2009;58:1375–81.PubMedCrossRef

32.

Madhaven D, Cuk K, Burwinkel B, et al. Cancer diagnosis and prognosis decoded by blood-based circulating microRNA signatures. Front Genet. 2013;4:116.

33.

Chang CY, Schiano TD. Drug hepatotoxicity. Aliment Pharmacol Ther. 2007;25:1135–51.PubMedCrossRef

34.

Halegoua-De Marzio D, Navarro VJ. Drug-induced hepatotoxicity in humans. Curr Opin Drug Discov Dev. 2008;11:53–9.

35.

Fannin RD, Russo M, O’Connell TM, et al. Acetaminophen dosing of humans results in blood transcriptome and metabolome changes consistent with impaired oxidative phosphorylation. Hepatology. 2010;51:227–36.PubMedCentralPubMedCrossRef

36.

Shi Q, Hong H, Senior J, et al. Biomarkers for drug-induced liver injury. Expert Rev Gastroenterol Hepatol. 2010;4:225–34.PubMedCrossRef

37.

Kim WR, Flamm SL, Di Bisceglie AM, et al. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology. 2008;47:1363–70.PubMedCrossRef

38.

Nathwani RA, Pais S, Reynolds TB, et al. Serum alanine aminotransferase in skeletal muscle diseases. Hepatology. 2005;41:380–2.PubMedCrossRef

39.

Antoine DJ, Williams DP, Jenkins AK, et al. High-mobility group box-1 protein and keratin-18, circulating serum proteins informative of acetaminophen-induced necrosis, and apoptosis in vivo. Toxicol Sci. 2009;112:521–31.PubMedCrossRef

40.

Boone L, Meyer D, Cusick P, et al. Selection and interpretation of clinical pathology indicators of hepatic injury in preclinical studies. Vet Clin Pathol. 2005;34:182–8.PubMedCrossRef

41.

Zhang Y, Jia Y, Zheng R, et al. Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin Chem. 2010;56:1830–8.PubMedCrossRef

42.

Antoine DJ, Mercer AE, Williams DP, et al. Mechanism-based bioanalysis and biomarkers for hepatic chemical stress. Xenobiotica. 2009;39:565–77.PubMedCrossRef

43.

Laterza OF, Lim L, Garrett-Engele PW, et al. Plasma microRNAs as sensitive and specific biomarkers of tissue injury. Clin Chem. 2009;55:1977–83.PubMedCrossRef

44.

Starkey Lewis PJ, Dear J, Platt V, et al. Circulating microRNA as potential markers of human drug-induced liver injury. Hepatology. 2011;54:1767–76.PubMedCrossRef

45.

Xu J, Wu C, Che X, et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog. 2011;50:136–42.PubMedCrossRef

46.

Bihrer V, Friedrich-Rust M, Kronenberger B, et al. Serum miR-122 as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection. Am J Gastroenterol. 2011;106:1663–9.PubMedCrossRef

47.

Cermelli S, Ruggieri A, Marrero J, et al. Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease. PLoS One. 2011;6:e23937.PubMedCentralPubMedCrossRef

48.

Yamamura Y, Nakajima M, Takagi S, et al. Plasma microRNA profiles in rat models of hepatocellular injury, cholestasis, and steatosis. PLoS One. 2012;7:e30250.CrossRef

49.

Bala S, Petrasek J, Mundkur S, et al. Circulating microRNAs in exosome indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology. 2012;56:1946–57.PubMedCentralPubMedCrossRef

50.

Yang X, Greenhaw J, Shi Q, et al. Identification of urinary microRNA profiles in rats that may diagnose hepatotoxicity. Toxicol Sci. 2012;125:335–44.PubMedCrossRef

51.

Fung M, Thornton A, Mybeck K, et al. Evaluation of the characteristics of safety withdrawal of prescription drugs from worldwide pharmaceutical markets: 1960 to 1999. Drug Inf J. 2001;35:293–317.

52.

de Winter RJ, Koster RW, Sturk A, et al. Value of myoglobin, troponin T, and CK-MB mass in ruling out an acute myocardial infarction in the emergency room. Circulation. 1995;92:3401–7.PubMedCrossRef

53.

Condrorelli G, Latronico MVG, Dorn GW. microRNA in heart disease: putative novel therapeutic targets? Eur Heart J. 2010;31:649–58.CrossRef

54.

Ji X, Takahashi R, Hiura Y, et al. Plasma miR-208 as a biomarker of myocardial injury. Clin Chem. 2009;55:1944–9.PubMedCrossRef

55.

Adams JE, Schechtman KB, Landt Y, et al. Comparable detection of acute myocardial infarction by creatine kinase MB isoenzyme and cardiac troponin I. Clin Chem. 1994;40:1291–5.PubMed

56.

Cheng Y, Tan N, Yang J, et al. A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci. 2010;119:87–95.PubMedCentralPubMedCrossRef

57.

Chen Y, Wang X, Yang J, et al. A translational study of urine miRNA in acute myocardial infarction. J Mol Cell Cardiol. 2012;53:668–76.PubMedCrossRef

58.

Wang GK, Zhu JQ, Zhang JT, et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J. 2010;31:659–66.PubMedCrossRef

59.

Corsten MF, Dennert R, Jochems S, et al. Circulating microRNA-208b and microRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet. 2010;3:499–506.PubMedCrossRef

60.

D’Alessandra Y, Devanna P, Limana F, et al. Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur Heart J. 2010;31:2765–73.PubMedCentralPubMedCrossRef

61.

Kuwabara Y, Ono K, Horie T, et al. Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate the existence of myocardial damage. Circ Cardiovasc Genet. 2011;4:446–54.PubMedCrossRef

62.

Adachi T, Nakanishi M, Otsuka Y, et al. Plasma microRNA 499 as a biomarker of acute myocardial infarction. Clin Chem. 2010;56:1183–5.PubMedCrossRef

63.

Oerlemans MIFJ, Mosterd A, Dekker MS, et al. Early assessment of acute coronary syndromes in the emergency department: the potential diagnostic value of circulating microRNAs. EMBO Mol Med. 2012;4:1176–85.PubMedCentralPubMedCrossRef

64.

Bustin SA, Benes V, Nolan T, et al. Quantitative real-time RT-PCR: a perspective. J Mol Endocrinol. 2005;34:597–601.PubMedCrossRef

65.

Peltier HJ, Latham GJ. Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues. RNA. 2008;14:844–52.PubMedCentralPubMedCrossRef

66.

Iwamoto H, Kanda Y, Sejima T, et al. Serum miR-210 as a potential biomarker of early clear cell renal cell carcinoma. Int J Oncol. 2013 (in press).

67.

Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105:10513–8.PubMedCentralPubMedCrossRef

68.

Guenin S, Mauriat M, Pelloux J, et al. Normalization of qRT-PCR data: the necessity of adopting a systematic, experimental conditions-specific, validation of references. J Exp Bot. 2009;60:487–93.PubMedCrossRef

69.

Song J, Bai Z, Han W, et al. Identification of suitable reference genes for qPCR analysis of serum microRNA in gastric cancer patients. Dig Dis Sci. 2012;57:897–904.PubMedCrossRef

70.

Wang Y, Tang N, Hui T, et al. Identification of endogenous reference genes for RT-qPCR analysis of plasma microRNAs levels in rats with acetaminophen-induced hepatotoxicity. J Appl Toxicol. 2013 (in press).

Titel: Circulating MicroRNAs in Drug Safety Assessment for Hepatic and Cardiovascular Toxicity: The Latest Biomarker Frontier?
verfasst von: Mitsuhiko Osaki
Nobuyoshi Kosaka
Futoshi Okada
Takahiro Ochiya
Publikationsdatum: 01.04.2014
Verlag: Springer International Publishing
Erschienen in: Molecular Diagnosis & Therapy / Ausgabe 2/2014
Print ISSN: 1177-1062
Elektronische ISSN: 1179-2000
DOI: https://doi.org/10.1007/s40291-013-0065-0

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2014

MicroRNA-499 rs3746444 Polymorphism and Autoimmune Diseases Risk: A Meta-Analysis

Circulating Melanoma Cells in the Diagnosis and Monitoring of Melanoma: An Appraisal of Clinical Potential

Biomarker Modelling of Early Molecular Changes in Alzheimer’s Disease

Association of E-Selectin Gene Polymorphism and Serum PAPP-A with Carotid Atherosclerosis in End-Stage Renal Disease

Sensitive Solid-Phase Detection of Donor-Specific Antibodies as an Aid Highly Relevant to Improving Allograft Outcomes