MicroRNAs as pharmacogenomic biomarkers for drug efficacy and drug safety assessment

Biomarkers in Medicine

Volumn 9, Issue 11, 2015, Pages 1153-1176

  Koturbash, Igor ^a   Tolleson, William H ^b   Guo, Lei ^b   Yu, Dianke ^b   Chen, Si ^b   Hong, Huixiao ^b   Mattes, William ^b   Ning, Baitang ^b  

^a UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

^b NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH   (United States)

Author keywords

biomarker; cardiotoxicity; drug efficacy; drug metabolizing enzymes; drug safety; hepatotoxicity; microRNA; nephrotoxicity

Indexed keywords

ABC TRANSPORTER A1; BIOLOGICAL MARKER; BREAST CANCER RESISTANCE PROTEIN; DRUG METABOLIZING ENZYME; GLUCOSE TRANSPORTER 3; MENKES PROTEIN; MICRORNA; MICRORNA 200C; MICRORNA 21; MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 1; MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 4; SUNITINIB;

APOPTOSIS; CANCER RESISTANCE; CANCER THERAPY; CARDIOTOXICITY; DIETARY INTAKE; DNA METHYLATION; DRUG EFFICACY; DRUG METABOLISM; DRUG RESPONSE; DRUG SAFETY; DRUG TRANSPORT; EPIGENETICS; EXOSOME; GENETIC VARIABILITY; HUMAN; KIDNEY CARCINOMA; LIVER TOXICITY; NEPHROTOXICITY; NONHUMAN; PANCREAS CANCER; PHARMACOGENOMICS; PROTEIN EXPRESSION; REVIEW; RISK ASSESSMENT; RNA ANALYSIS; RNA TRANSPORT; TOXIC HEPATITIS; TRANSCRIPTION REGULATION; ANIMAL; DRUG RESISTANCE; GENETICS; METABOLISM; PHARMACOGENETICS; PROCEDURES; SAFETY;

ANIMALS; BIOMARKERS; DRUG RESISTANCE, NEOPLASM; HUMANS; MICRORNAS; PHARMACOGENETICS; SAFETY;

EID: 84947778751     PISSN: 17520363     EISSN: 17520371     Source Type: Journal    
DOI: 10.2217/bmm.15.89     Document Type: Review

References (239)

1. Krek A, Grun D, Poy MN et al. Combinatorial microRNA target predictions. Nature Genet. 37(5), 495-500 (2005).
2. Esteller M. Non-coding RNAs in human disease. Nat. Rev. Genet. 12(12), 861-874 (2011).
3. Di Leva G, Garofalo M, Croce CM. MicroRNAs in cancer. Ann. Rev. Pathol. 9 287-314 (2014).
4. Vidigal JA, Ventura A. The biological functions of miRNAs: lessons from in vivo studies. Trends Cell Biol. 25(3), 137-147 (2015).
5. Doench JG, Sharp PA. Specificity of microRNA target selection in translational repression. Genes Develop. 18(5), 504-511 (2004).
6. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 136(2), 215-233 (2009).
7. Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19(1), 92-105 (2009).
8. Koturbash I, Beland FA, Pogribny IP. Role of microRNAs in the regulation of drug metabolizing and transporting genes and the response to environmental toxicants. Expert Opin. Drug Metab. Toxicol. 8(5), 597-606 (2012).
9. Yokoi T, Nakajima M. microRNAs as mediators of drug toxicity. Ann. Rev. Pharmacol. Toxicol. 53 377-400 (2013).
10. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat. Rev. Cancer 6(11), 857-866 (2006).
11. Xie B, Ding Q, Han H, Wu D. miRCancer: a microRNAcancer association database constructed by text mining on literature. Bioinformatics 29(5), 638-644 (2013).
12. Ikeda S, Kong SW, Lu J et al. Altered microRNA expression in human heart disease. Physiol. Genomics 31(3), 367-373 (2007).
13. Zhou R, Yuan P, Wang Y et al. Evidence for selective microRNAs and their effectors as common long-term targets for the actions of mood stabilizers. Neuropsychopharmacol. 34(6), 1395-1405 (2009).
14. Zampetaki A, Mayr M. MicroRNAs in vascular and metabolic disease. Circ. Res. 110(3), 508-522 (2012).
15. Iorio MV, Croce CM. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol. Med. 4(3), 143-159 (2012).
16. Van Rooij E, Purcell AL, Levin AA. Developing microRNA therapeutics. Circ. Res. 110(3), 496-507 (2012).
17. Wilkinson GR. Drug metabolism and variability among patients in drug response. N. Engl. J. Med. 352(21), 2211-2221 (2005).
18. Spear BB, Heath-Chiozzi M, Huff J. Clinical application of pharmacogenetics. Trends Mol. Med. 7(5), 201-204 (2001).
19. Constable S, Johnson MR, Pirmohamed M. Pharmacogenetics in clinical practice: considerations for testing. Expert Rev. Mol. Diagn. 6(2), 193-205 (2006).
20. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 279(15), 1200-1205 (1998).
21. Waxman DJ, Holloway MG. Sex differences in the expression of hepatic drug metabolizing enzymes. Mol. Pharmacol. 76(2), 215-228 (2009).
22. Yang L, Price ET, Chang CW et al. Gene expression variability in human hepatic drug metabolizing enzymes and transporters. PLoS ONE 8(4), e60368 (2013).
23. Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286(5439), 487-491 (1999).
24. Ma MK, Woo MH, Mcleod HL. Genetic basis of drug metabolism. Am. J. Health Syst. Pharm. 59(21), 2061-2069 (2002).
25. Zhou SF, Liu JP, Chowbay B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab. Rev. 41(2), 89-295 (2009).
26. Ingelman-Sundberg M, Zhong XB, Hankinson O et al. Potential role of epigenetic mechanisms in the regulation of drug metabolism and transport. Drug Metab. Dispos. 41(10), 1725-1731 (2013).
27. Yu AM. Role of microRNAs in the regulation of drug metabolism and disposition. Expert Opin. Drug Metab. Toxicol. 5(12), 1513-1528 (2009).
28. Nakajima M, Yokoi T. MicroRNAs from biology to future pharmacotherapy: regulation of cytochrome P450s and nuclear receptors. Pharmacol. Ther. 131(3), 330-337 (2011).
29. He Y, Chevillet JR, Liu G, Kim TK, Wang K. The effects of microRNA on the absorption, distribution, metabolism and excretion of drugs. Br. J. Pharmacol. doi:10. 1111/bph. 12968 (2014) (Epub ahead of print).
30. Maglich JM, Stoltz CM, Goodwin B, Hawkins-Brown D, Moore JT, Kliewer SA. Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Mol. Pharmacol. 62(3), 638-646 (2002).
31. Lehmann JM, Mckee DD, Watson MA, Willson TM, Moore JT, Kliewer SA. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J. Clin. Invest. 102(5), 1016-1023 (1998).
32. Hayes JD, Pulford DJ. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit. Rev. Biochem. Mol. Biol. 30(6), 445-600 (1995).
33. Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol. Ther. 138(1), 103-141 (2013).
34. Jigorel E, Le Vee M, Boursier-Neyret C, Parmentier Y, Fardel O. Differential regulation of sinusoidal and canalicular hepatic drug transporter expression by xenobiotics activating drug-sensing receptors in primary human hepatocytes. Drug Metab. Dispos. 34(10), 1756-1763 (2006).
35. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat. Rev. Genet. 11(9), 597-610 (2010).
36. Ning B, Su Z, Mei N et al. Toxicogenomics and cancer susceptibility: advances with next-generation sequencing. J. Environ. Sci. Health C. Environ. Carcinog. Ecotoxicol. Rev. 32(2), 121-158 (2014).
37. Gaedicke S, Zhang X, Schmelzer C et al. Vitamin E dependent microRNA regulation in rat liver. FEBS Lett. 582(23-24), 3542-3546 (2008).
38. Tryndyak VP, Ross SA, Beland FA, Pogribny IP. Downregulation of the microRNAs miR-34a, miR-127, and miR-200b in rat liver during hepatocarcinogenesis induced by a methyl-deficient diet. Mol. Carcinog. 48(6), 479-487 (2009).
39. Li Y, Kong D, Wang Z, Sarkar FH. Regulation of microRNAs by natural agents: an emerging field in chemoprevention and chemotherapy research. Pharm. Res. 27(6), 1027-1041 (2010).
40. Omiecinski CJ, Vanden Heuvel JP, Perdew GH, Peters JM. Xenobiotic metabolism, disposition, and regulation by receptors: from biochemical phenomenon to predictors of major toxicities. Toxicol. Sci. 120(Suppl. 1), S49-S75 (2011).
41. Tirona RG, Kim RB. Nuclear receptors and drug disposition gene regulation. J. Pharm. Sci. 94(6), 1169-1186 (2005).
42. Bolleyn J, De Kock J, Rodrigues RM, Vinken M, Rogiers V, Vanhaecke T. MicroRNAs as key regulators of xenobiotic biotransformation and drug response. Arch. Toxicol. doi:10. 1007/s00204-014-1314-7 (2014) (Epub ahead of print).
43. Takwi AA, Wang YM, Wu J, Michaelis M, Cinatl J, Chen T. miR-137 regulates the constitutive androstane receptor and modulates doxorubicin sensitivity in parental and doxorubicin-resistant neuroblastoma cells. Oncogene 33(28), 3717-3729 (2014).
44. Zhong XB, Leeder JS. Epigenetic regulation of ADMErelated genes: focus on drug metabolism and transport. Drug Metab. Dispos. 41(10), 1721-1724 (2013).
45. Rieger JK, Klein K, Winter S, Zanger UM. Expression variability of absorption, distribution, metabolism, excretionrelated microRNAs in human liver: influence of nongenetic factors and association with gene expression. Drug Metab. Dispos. 41(10), 1752-1762 (2013).
46. Tsuchiya Y, Nakajima M, Takagi S, Taniya T, Yokoi T. MicroRNA regulates the expression of human cytochrome P450 1B1. Cancer Res. 66(18), 9090-9098 (2006).
47. Yu X, Dhakal IB, Beggs M et al. Functional genetic variants in the 3'-untranslated region of sulfotransferase isoform 1A1 (SULT1A1) and their effect on enzymatic activity. Toxicol. Sci. 118(2), 391-403 (2010).
48. Yu D, Green B, Marrone A et al. Suppression of CYP2C9 by microRNA hsa-miR-128-3p in human liver cells and association with hepatocellular carcinoma. Sci. Rep. 5, 8534 (2015).
49. Rukov JL, Shomron N. MicroRNA pharmacogenomics: post-transcriptional regulation of drug response. Trends Mol. Med. 17(8), 412-423 (2011).
50. Kacevska M, Ivanov M, Ingelman-Sundberg M. Epigeneticdependent regulation of drug transport and metabolism: an update. Pharmacogenomics 13(12), 1373-1385 (2012).
51. Kim IW, Han N, Burckart GJ, Oh JM. Epigenetic changes in gene expression for drug-metabolizing enzymes and transporters. Pharmacotherapy 34(2), 140-150 (2014).
52. Liu C, Zhang F, Li T et al. MirSNP, a database of polymorphisms altering miRNA target sites, identifies miRNA-related SNPs in GWAS SNPs and eQTLs. BMC Genomics 13 661 (2012).
53. Bhattacharya A, Ziebarth JD, Cui Y. PolymiRTS Database 3. 0: linking polymorphisms in microRNAs and their target sites with human diseases and biological pathways. Nucleic Acids Res. 42(Database issue), D86-D91 (2014).
54. Crespi CL, Miller VP. The R144C change in the CYP2C9 2 allele alters interaction of the cytochrome P450 with NADPH:cytochrome P450 oxidoreductase. Pharmacogenetics 7(3), 203-210 (1997).
55. Raftogianis RB, Wood TC, Weinshilboum RM. Human phenol sulfotransferases SULT1A2 and SULT1A1: genetic polymorphisms, allozyme properties, and human liver genotype-phenotype correlations. Biochem. Pharmacol. 58(4), 605-616 (1999).
56. Ning B, Nowell S, Sweeney C et al. Common genetic polymorphisms in the 5'-flanking region of the SULT1A1 gene: haplotypes and their association with platelet enzymatic activity. Pharmacogenet. Genom. 15(7), 465-473 (2005).
57. Hebbring SJ, Adjei AA, Baer JL et al. Human SULT1A1 gene: copy number differences and functional implications. Hum. Mol. Genet. 16(5), 463-470 (2007).
58. Stehle F, Schulz K, Seliger B. Towards defining biomarkers indicating resistances to targeted therapies. BBA Prot. Proteom. 1844(5), 909-916 (2014).
59. Brown R, Curry E, Magnani L, Wilhelm-Benartzi CS, Borley J. Poised epigenetic states and acquired drug resistance in cancer. Nat. Rev. Cancer 14(11), 747-753 (2014).
60. Burrell RA, Swanton C. Tumour heterogeneity and the evolution of polyclonal drug resistance. Mol. Oncol. 8(6), 1095-1111 (2014).
61. Pommier Y, Sordet O, Antony S, Hayward RL, Kohn KW. Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks. Oncogene 23(16), 2934-2949 (2004).
62. Casorelli I, Bossa C, Bignami M. DNA damage and repair in human cancer: molecular mechanisms and contribution to therapy-related leukemias. Int. J. Environ. Res. Public Health 9(8), 2636-2657 (2012).
63. Starczynski J, Pepper C, Pratt G et al. Common polymorphism G(-248)A in the promoter region of the bax gene results in significantly shorter survival in patients with chronic lymphocytic Leukemia once treatment is initiated. J. Clin. Oncol. 23(7), 1514-1521 (2005).
64. Mishra PJ, Humeniuk R, Mishra PJ, Longo-Sorbello GSA, Banerjee D, Bertino JR. A miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance. Proc. Natl Acad. Sci. USA 104(33), 13513-13518 (2007).
65. Goto Y, Yue L, Yokoi A et al. A novel single-nucleotide polymorphism in the 3'-untranslated region of the human dihydrofolate reductase gene with enhanced expression. Clin. Cancer Res. 7(7), 1952-1956 (2001).
66. Nowell PC. The clonal evolution of tumor cell populations. Science 194(4260), 23-28 (1976).
67. Bakhoum SF, Compton DA. Chromosomal instability and cancer: a complex relationship with therapeutic potential. J. Clin. Invest. 122(4), 1138-1143 (2012).
68. Zheng TS, Wang JB, Chen X, Liu LX. Role of microRNA in anticancer drug resistance. Int. J. Cancer 126(1), 2-10 (2010).
69. Dai X, Tan C. Combination of microRNA therapeutics with small-molecule anticancer drugs: mechanism of action and co-delivery nanocarriers. Adv. Drug Deliv. Rev. 81 184-197 (2015).
70. Cellini F, Morganti AG, Genovesi D, Silvestris N, Valentini V. Role of microRNA in response to ionizing radiations: evidences and potential impact on clinical practice for radiotherapy. Molecules 19(4), 5379-5401 (2014).
71. De Rosa F, Fanini F, Guidoboni M et al. MicroRNAs and dendritic cell-based vaccination in melanoma patients. Melanoma Res. 24(3), 181-189 (2014).
72. Kitamura T, Taketo MM. Keeping out the bad guys: gateway to cellular target therapy. Cancer Res. 67(21), 10099-10102 (2007).
73. Kosaka N, Yoshioka Y, Tominaga N, Hagiwara K, Katsuda T, Ochiya T. Dark side of the exosome: the role of the exosome in cancer metastasis and targeting the exosome as a strategy for cancer therapy. Future Oncol. 10(4), 671-681 (2014).
74. Zhao L, Liu WT, Xiao J, Cao BW. The role of exosomes and "exosomal shuttle microRNA" in tumorigenesis and drug resistance. Cancer Lett. 356(2), 339-346 (2015).
75. Chen WX, Liu XM, Lv MM et al. Exosomes from drugresistant breast cancer cells transmit chemoresistance by a horizontal transfer of microRNAs. PLoS ONE 9(4), e95240 (2014).
76. Wang JH, Hendrix A, Hernot S et al. Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells. Blood 124(4), 555-566 (2014).
77. Umezu T, Ohyashiki K, Kuroda M, Ohyashiki JH. Leukemia cell to endothelial cell communication via exosomal miRNAs. Oncogene 32(22), 2747-2755 (2013).
78. Bao LL, Hazari S, Mehra S, Kaushal D, Moroz K, Dash S. Increased expression of P-glycoprotein and doxorubicin chemoresistance of metastatic breast cancer is regulated by miR-298. Am. J. Pathol. 180(6), 2490-2503 (2012).
79. Kovalchuk O, Filkowski J, Meservy J et al. Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol. Cancer Ther. 7(7), 2152-2159 (2008).
80. Feng DD, Zhang H, Zhang P et al. Down-regulated miR-331-5p and miR-27a are associated with chemotherapy resistance and relapse in leukaemia. J. Cell. Mol. Med. 15(10), 2164-2175 (2011).
81. Wu Q, Yang ZP, Xia L et al. Methylation of miR-129-5p CpG island modulates multi-drug resistance in gastric cancer by targeting ABC transporters. Oncotarget 5(22), 11552-11563 (2014).
82. Boyerinas B, Park SM, Murmann AE et al. Let-7 modulates acquired resistance of ovarian cancer to Taxanes via IMP-1-mediated stabilization of multidrug resistance 1. Int. J. Cancer 130(8), 1787-1797 (2012).
83. Yang LY, Li NW, Wang HJ, Jia XB, Wang X, Luo J. Altered microRNA expression in cisplatin-resistant ovarian cancer cells and upregulation of miR-130a associated with MDR1/P-glycoprotein-mediated drug resistance. Oncol. Rep. 28(2), 592-600 (2012).
84. Hong L, Han Y, Zhang H et al. The prognostic and chemotherapeutic value of miR-296 in esophageal squamous cell carcinoma. Ann. Surg. 251(6), 1056-1063 (2010).
85. Turrini E, Haenisch S, Laechelt S, Diewock T, Bruhn O, Cascorbi I. MicroRNA profiling in K-562 cells under imatinib treatment: influence of miR-212 and miR-328 on ABCG2 expression. Pharmacogenet. Genomics 22(3), 198-205 (2012).
86. Pan YZ, Morris ME, Yu AM. MicroRNA-328 negatively regulates the expression of breast cancer resistance protein (BCRP/ABCG2) in human cancer cells. Mol. Pharmacol. 75(6), 1374-1379 (2009).
87. Dong Z, Zhong Z, Yang L, Wang S, Gong Z. MicroRNA-31 inhibits cisplatin-induced apoptosis in non-small cell lung cancer cells by regulating the drug transporter ABCB9. Cancer Lett. 343(2), 249-257 (2014).
88. Song LQ, Li Y, Li WN, Wu SZ, Li ZK. miR-495 Enhances the Sensitivity of non-small cell lung cancer cells to platinum by modulation of copper transporting P-type adenosine triphosphatase A (ATP7A). J. Cell. Biochem. 115(7), 1234-1242 (2014).
89. Zong C, Wang J, Shi TM. MicroRNA 130b enhances drug resistance in human ovarian cancer cells. Tumor Biol. 35(12), 12151-12156 (2014).
90. Raynal C, Pascussi JM, Legueline G et al. Pregnane x Receptor (PXR) expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation. Mol. Cancer 9 13 (2010).
91. Takagi S, Nakajima M, Mohri T, Yokoi T. Posttranscriptional regulation of human pregnane x receptor by micro-RNA affects the expression of cytochrome P450 3A4. J. Biol. Chem. 283(15), 9674-9680 (2008).
92. Lobert S, Jefferson B, Morris K. Regulation of beta-tubulin isotypes by Micro-RNA 100 in MCF7 breast cancer cells. Cytoskeleton 68(6), 355-362 (2011).
93. Xia L, Zhang D, Du R et al. miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int. J. Cancer 123(2), 372-379 (2008).
94. Zimmerman EI, Dollins CM, Crawford M et al. Lyn kinase-dependent regulation of miR181 and myeloid cell leukemia-1 expression: implications for drug resistance in myelogenous leukemia. Mol. Pharmacol. 78(5), 811-817 (2010).
95. Yang H, Kong W, He L et al. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res 68(2), 425-433 (2008).
96. Chen Y, Tsai YH, Fang Y, Tseng SH. Micro-RNA-21 regulates the sensitivity to cisplatin in human neuroblastoma cells. J. Pediatr. Surg. 47(10), 1797-1805 (2012).
97. Garofalo M, Di Leva G, Romano G et al. miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. 16(6), 498-509 (2009).
98. Fu X, Tian J, Zhang L, Chen Y, Hao Q. Involvement of microRNA-93, a new regulator of PTEN/Akt signaling pathway, in regulation of chemotherapeutic drug cisplatin chemosensitivity in ovarian cancer cells. FEBS Lett. 586(9), 1279-1286 (2012).
99. Le Sage C, Nagel R, Egan DA et al. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J. 26(15), 3699-3708 (2007).
100. Miller TE, Ghoshal K, Ramaswamy B et al. MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J. Biol. Chem. 283(44), 29897-29903 (2008).
101. Garofalo M, Quintavalle C, Di Leva G et al. MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer. Oncogene 27(27), 3845-3855 (2008).
102. Marrone AK, Beland FA, Pogribny IP. The role for microRNAs in drug toxicity and in safety assessment. Expert Opin. Drug Metab. Toxicol. 11(4), 601-611 (2015).
103. Boon RA, Vickers KC. Intercellular transport of microRNAs. Arterioscleros. Thromb. Vasc. Biol. 33(2), 186-192 (2013).
104. Ajit SK. Circulating microRNAs as biomarkers, therapeutic targets, and signaling molecules. Sensors 12(3), 3359-3369 (2012).
105. Cogswell JP, Ward J, Taylor IA et al. Identification of miRNA changes in Alzheimer's disease brain and CSF yields putative biomarkers and insights into disease pathways. J. Alzheimer. Dis. 14(1), 27-41 (2008).
106. Gallo A, Tandon M, Alevizos I, Illei GG. The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS ONE 7(3), e30679 (2012).
107. Kosaka N, Izumi H, Sekine K, Ochiya T. microRNA as a new immune-regulatory agent in breast milk. Silence 1(1), 7 (2010).
108. Wang C, Yang C, Chen X et al. Altered profile of seminal plasma microRNAs in the molecular diagnosis of male infertility. Clin. Chem. 57(12), 1722-1731 (2011).
109. Zhang J, Zhao H, Gao Y, Zhang W. Secretory miRNAs as novel cancer biomarkers. Biochim. Biophys. Acta 1826(1), 32-43 (2012).
110. Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids-the mix of hormones and biomarkers. Nat. Rev. Clin. Oncol. 8(8), 467-477 (2011).
111. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9(6), 654-659 (2007).
112. Mikaelian I, Scicchitano M, Mendes O, Thomas RA, Leroy BE. Frontiers in preclinical safety biomarkers: microRNAs and messenger RNAs. Toxicol. Pathol. 41(1), 18-31 (2013).
113. Raza U, Zhang JD, Sahin O. MicroRNAs: master regulators of drug resistance, stemness, and metastasis. J. Mol. Med. 92(4), 321-336 (2014).
114. Price C, Chen J. MicroRNAs in cancer biology and therapy: current status and perspectives. Genes Dis. 1(1), 53-63 (2014).
115. Yamashita D, Kondo T, Ohue S et al. miR340 suppresses the stem-like cell function of glioma-initiating cells by targeting tissue plasminogen activator. Cancer Res. 75(6), 1123-1133 (2015).
116. Koturbash I, Zemp FJ, Pogribny I, Kovalchuk O. Small molecules with big effects: the role of the microRNAome in cancer and carcinogenesis. Mutat. Res. 722(2), 94-105 (2011).
117. Gao W, Lu X, Liu L, Xu J, Feng D, Shu Y. MiRNA-21: a biomarker predictive for platinum-based adjuvant chemotherapy response in patients with non-small cell lung cancer. Cancer Biol. Ther. 13(5), 330-340 (2012).
118. Hwang JH, Voortman J, Giovannetti E et al. Identification of microRNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer. PLoS ONE 5(5), e10630 (2010).
119. Pan X, Wang ZX, Wang R. MicroRNA-21: a novel therapeutic target in human cancer. Cancer Biol. Ther. 10(12), 1224-1232 (2010).
120. Sinha M, Ghatak S, Roy S, Sen CK. microRNA-200b as a switch for inducible adult angiogenesis. Antiox. Redox Signal. doi:10. 1089/ars. 2014. 6065 (2015) (Epub ahead of print).
121. Pecot CV, Rupaimoole R, Yang D et al. Tumour angiogenesis regulation by the miR-200 family. Nat. Comm. 4, 2427 (2013).
122. Zhu W, Xu H, Zhu D et al. miR-200bc/429 cluster modulates multidrug resistance of human cancer cell lines by targeting BCL2 and XIAP. Cancer Chemother. Pharmacol. 69(3), 723-731 (2012).
123. Rui W, Bing F, Hai-Zhu S, Wei D, Long-Bang C. Identification of microRNA profiles in docetaxel-resistant human non-small cell lung carcinoma cells (SPC-A1). J. Cell. Mol. Med. 14(1-2), 206-214 (2010).
124. Feng B, Wang R, Song HZ, Chen LB. MicroRNA-200b reverses chemoresistance of docetaxel-resistant human lung adenocarcinoma cells by targeting E2F3. Cancer 118(13), 3365-3376 (2012).
125. Olson P, Lu J, Zhang H et al. MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer. Genes Develop. 23(18), 2152-2165 (2009).
126. Passadouro M, Pedroso De Lima MC, Faneca H. MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer. Int. J. Nanomed. 9 3203-3217 (2014).
127. Costa PM, Cardoso AL, Pereira De Almeida LF, Bruce JN, Canoll P, Pedroso De Lima MC. PDGF-B-mediated downregulation of miR-21: new insights into PDGF signaling in glioblastoma. Hum. Mol. Genet. 21(23), 5118-5130 (2012).
128. Berkers J, Govaere O, Wolter P et al. A possible role for microRNA-141 down-regulation in sunitinib resistant metastatic clear cell renal cell carcinoma through induction of epithelial-to-mesenchymal transition and hypoxia resistance. J. Urol. 189(5), 1930-1938 (2013).
129. Prior C, Perez-Gracia JL, Garcia-Donas J et al. Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma. PLoS ONE 9(1), e86263 (2014).
130. Gamez-Pozo A, Anton-Aparicio LM, Bayona C et al. MicroRNA expression profiling of peripheral blood samples predicts resistance to first-line sunitinib in advanced renal cell carcinoma patients. Neoplasia 14(12), 1144-1152 (2012).
131. Shivapurkar N, Mikhail S, Navarro R et al. Decrease in blood miR-296 predicts chemotherapy resistance and poor clinical outcome in patients receiving systemic chemotherapy for metastatic colon cancer. Int. J. Colorect. Dis. 28(6), 887 (2013).
132. Fujioka S, Nakamichi I, Esaki M, Asano K, Matsumoto T, Kitazono T. Serum microRNA levels in patients with Crohn's disease during induction therapy by infliximab. J. Gastroenterol. Hepatol. 29(6), 1207-1214 (2014).
133. De Iudicibus S, Lucafo M, Martelossi S, Pierobon C, Ventura A, Decorti G. MicroRNAs as tools to predict glucocorticoid response in inflammatory bowel diseases. World J. Gastroenterol. 19(44), 7947-7954 (2013).
134. Papaconstantinou I, Stamatis K, Tzathas C, Vassiliou I, Giokas G, Gazouli M. The role of variations within microRNA in inflammatory bowel disease. Eur. J. Gastroenterol. Hepatol. 25(4), 399-403 (2013).
135. Lee WM. Drug-induced hepatotoxicity. N. Engl. J. Med. 349(5), 474-485 (2003).
136. Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology 245(3), 194-205 (2008).
137. Shabaneh Al-Tamimi HA, Mcdonald R. Elevated alanine aminotransferase levels associated with polymyositis: can this be due to muscle injury? J. Clin. Rheumatol. 14(6), 363-364 (2008).
138. Antoine DJ, Dear JW, Lewis PS et al. Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital. Hepatology 58(2), 777-787 (2013).
139. Buness A, Roth A, Herrmann A et al. Identification of metabolites, clinical chemistry markers and transcripts associated with hepatotoxicity. PLoS ONE 9(5), e97249 (2014).
140. Campion S, Aubrecht J, Boekelheide K et al. The current status of biomarkers for predicting toxicity. Expert Opin. Drug Metab. Toxicol. 9(11), 1391-1408 (2013).
141. Starkey Lewis PJ, Dear J, Platt V et al. Circulating microRNAs as potential markers of human drug-induced liver injury. Hepatology 54(5), 1767-1776 (2011).
142. Laterza OF, Lim L, Garrett-Engele PW et al. Plasma MicroRNAs as sensitive and specific biomarkers of tissue injury. Clin. Chem. 55(11), 1977-1983 (2009).
143. Ding X, Ding J, Ning J et al. Circulating microRNA-122 as a potential biomarker for liver injury. Mol. Med. Report doi:10. 3892/mmr. 2012. 838 (2012) (Epub ahead of print).
144. Fukushima T, Hamada Y, Yamada H, Horii I. Changes of micro-RNA expression in rat liver treated by acetaminophen or carbon tetrachloride regulating role of micro-RNA for RNA expression. J. Toxicol. Sci. 32(4), 401-409 (2007).
145. Krauskopf J, Caiment F, Claessen SM et al. Application of high-throughput sequencing to circulating microRNAs reveals novel biomarkers for drug-induced liver injury. Toxicol. Sci. 143(2), 268-276 (2015).
146. Moffat ID, Boutros PC, Celius T, Linden J, Pohjanvirta R, Okey AB. microRNAs in adult rodent liver are refractory to dioxin treatment. Toxicol. Sci. 99(2), 470-487 (2007).
147. Pogribny IP, Tryndyak VP, Boyko A, Rodriguez-Juarez R, Beland FA, Kovalchuk O. Induction of microRNAome deregulation in rat liver by long-term tamoxifen exposure. Mutat. Res. 619(1-2), 30-37 (2007).
148. Su YW, Chen X, Jiang ZZ et al. A panel of serum microRNAs as specific biomarkers for diagnosis of compound-and herb-induced liver injury in rats. PLoS ONE 7(5), e37395 (2012).
149. Ward J, Kanchagar C, Veksler-Lublinsky I et al. Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis. Proc. Natl Acad. Sci. USA 111(33), 12169-12174 (2014).
150. Yamaura Y, Nakajima M, Takagi S, Fukami T, Tsuneyama K, Yokoi T. Plasma microRNA profiles in rat models of hepatocellular injury, cholestasis, and steatosis. PLoS ONE 7(2), e30250 (2012).
151. 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. 31(6), 659-666 (2010).
152. Ward J, Bala S, Petrasek J, Szabo G. Plasma microRNA profiles distinguish lethal injury in acetaminophen toxicity: a research study. World J. Gastroenterol. 18(22), 2798-2804 (2012).
153. Wang K, Zhang S, Marzolf B et al. Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc. Natl Acad. Sci. USA 106(11), 4402-4407 (2009).
154. Osaki M, Kosaka N, Okada F, Ochiya T. Circulating microRNAs in drug safety assessment for hepatic and cardiovascular toxicity: the latest biomarker frontier? Mol. Diagn. Ther. 18(2), 121-126 (2014).
155. Broder H, Gottlieb RA, Lepor NE. Chemotherapy and cardiotoxicity. Rev. Cardiovasc. Med. 9(2), 75-83 (2008).
156. Leishman DJ, Beck TW, Dybdal N et al. Best practice in the conduct of key nonclinical cardiovascular assessments in drug development: current recommendations from the Safety Pharmacology Society. J. Pharmacol. Toxicol. Methods 65(3), 93-101 (2012).
157. Sarazan RD, Mittelstadt S, Guth B, Koerner J, Zhang J, Pettit S. Cardiovascular function in nonclinical drug safety assessment: current issues and opportunities. Int. J. Toxicol. 30(3), 272-286 (2011).
158. Raschi E, Ceccarini L, De Ponti F, Recanatini M. hERGrelated drug toxicity and models for predicting hERG liability and QT prolongation. Expert Opin. Drug Metab. Toxicol. 5(9), 1005-1021 (2009).
159. Shah RR. Can pharmacogenetics help rescue drugs withdrawn from the market? Pharmacogenomics 7(6), 889-908 (2006).
160. Liu L, Aguirre SA, Evering WE et al. miR-208a as a biomarker of isoproterenol-induced cardiac injury in Sod2+/-and C57BL/6J wild-type mice. Toxicol. Pathol. 42(7), 1117-1129 (2014).
161. Sandhu H, Maddock H. Molecular basis of cancer-therapyinduced cardiotoxicity: introducing microRNA biomarkers for early assessment of subclinical myocardial injury. Clin. Sci. 126(6), 377-400 (2014).
162. From AM, Maleszewski JJ, Rihal CS. Current status of endomyocardial biopsy. Mayo Clin. Proc. 86(11), 1095-1102 (2011).
163. Collinson PO, Boa FG, Gaze DC. Measurement of cardiac troponins. Ann. Clin. Biochem. 38(Pt 5), 423-449 (2001).
164. Reagan WJ. Troponin as a biomarker of cardiac toxicity: past, present, and future. Toxicol. Pathol. 38(7), 1134-1137 (2010).
165. Tonomura Y, Matsushima S, Kashiwagi E et al. Biomarker panel of cardiac and skeletal muscle troponins, fatty acid binding protein 3 and myosin light chain 3 for the accurate diagnosis of cardiotoxicity and musculoskeletal toxicity in rats. Toxicology 302(2-3), 179-189 (2012).
166. Ji X, Takahashi R, Hiura Y, Hirokawa G, Fukushima Y, Iwai N. Plasma miR-208 as a biomarker of myocardial injury. Clin. Chem. 55(11), 1944-1949 (2009).
167. Nishimura Y, Kondo C, Morikawa Y et al. Plasma miR-208 as a useful biomarker for drug-induced cardiotoxicity in rats. J. Appl. Toxicol. 35(2), 173-180 (2015).
168. Desai VG, J CK, Vijay V et al. Early biomarkers of doxorubicin-induced heart injury in a mouse model. Toxicol. Appl. Pharmacol. 281(2), 221-229 (2014).
169. Condorelli G, Latronico MV, Dorn GW 2nd. microRNAs in heart disease: putative novel therapeutic targets? Eur. Heart J. 31(6), 649-658 (2010).
170. Horie T, Ono K, Nishi H et al. Acute doxorubicin cardiotoxicity is associated with miR-146a-induced inhibition of the neuregulin-ErbB pathway. Cardiovasc. Res. 87(4), 656-664 (2010).
171. Chen B, Peng X, Pentassuglia L, Lim CC, Sawyer DB. Molecular and cellular mechanisms of anthracycline cardiotoxicity. Cardiovasc. Toxicol. 7(2), 114-121 (2007).
172. Vacchi-Suzzi C, Hahne F, Scheubel P et al. Heart structurespecific transcriptomic atlas reveals conserved microRNAmRNA interactions. PLoS ONE 8(1), e52442 (2013).
173. Mishra J, Dent C, Tarabishi R et al. Neutrophil gelatinaseassociated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365(9466), 1231-1238 (2005).
174. Dieterle F, Sistare F, Goodsaid F et al. Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium. Nat. Biotechnol. 28(5), 455-462 (2010).
175. Bhatt K, Zhou L, Mi QS, Huang S, She JX, Dong Z. MicroRNA-34a is induced via p53 during cisplatin nephrotoxicity and contributes to cell survival. Mol. Med. 16(9-10), 409-416 (2010).
176. Kanki M, Moriguchi A, Sasaki D et al. Identification of urinary miRNA biomarkers for detecting cisplatin-induced proximal tubular injury in rats. Toxicology 324 158-168 (2014).
177. Saikumar J, Hoffmann D, Kim TM et al. Expression, circulation, and excretion profile of microRNA-21,-155, and-18a following acute kidney injury. Toxicol. Sci. 129(2), 256-267 (2012).
178. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5), 843-854 (1993).
179. Ambros V. microRNAs: tiny regulators with great potential. Cell 107(7), 823-826 (2001).
180. Reinhart BJ, Slack FJ, Basson M et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403(6772), 901-906 (2000).
181. Krichevsky AM, King KS, Donahue CP, Khrapko K, Kosik KS. A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9(10), 1274-1281 (2003).
182. Ishizuka A, Siomi MC, Siomi H. A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes Dev. 16(19), 2497-2508 (2002).
183. Caudy AA, Myers M, Hannon GJ, Hammond SM. Fragile X-related protein and VIG associate with the RNA interference machinery. Genes Dev. 16(19), 2491-2496 (2002).
184. Calin GA, Dumitru CD, Shimizu M et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc. Natl Acad. Sci. USA 99(24), 15524-15529 (2002).
185. Mcmanus MT. MicroRNAs and cancer. Semin Cancer Biol 13(4), 253-258 (2003).
186. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr. Biol. 12(9), 735-739 (2002).
187. Yang Q, Nagano T, Shah Y, Cheung C, Ito S, Gonzalez FJ. The PPAR alpha-humanized mouse: a model to investigate species differences in liver toxicity mediated by PPAR alpha. Toxicol. Sci. 101(1), 132-139 (2008).
188. Wong N, Wang X. miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res. 43(Database issue), D146-D152 (2015).
189. Hsu SD, Tseng YT, Shrestha S et al. miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions. Nucleic Acids Res. 42(Database issue), D78-D85 (2014).
190. Dweep H, Sticht C, Pandey P, Gretz N. miRWalk-database: prediction of possible miRNA binding sites by "walking" the genes of three genomes. J. Biomed. Inform. 44(5), 839-847 (2011).
191. Kaya KD, Karakulah G, Yakicier CM, Acar AC, Konu O. mESAdb: microRNA expression and sequence analysis database. Nucleic Acids Res. 39(Database issue), D170-D180 (2011).
192. Yang JH, Shao P, Zhou H, Chen YQ, Qu LH. deepBase: a database for deeply annotating and mining deep sequencing data. Nucleic Acids Res. 38(Database issue), D123-D130 (2010).
193. Alexiou P, Vergoulis T, Gleditzsch M et al. miRGen 2. 0: a database of microRNA genomic information and regulation. Nucleic Acids Res. 38(Database issue), D137-D141 (2010).
194. Jiang Q, Wang Y, Hao Y et al. miR2Disease: a manually curated database for microRNA deregulation in human disease. Nucleic Acids Res. 37(Database issue), D98-D104 (2009).
195. Betel D, Wilson M, Gabow A, Marks DS, Sander C. The microRNA. org resource: targets and expression. Nucleic Acids Res. 36(Database issue), D149-D153 (2008).
196. Griffiths-Jones S, Saini HK, Van Dongen S, Enright AJ. miRBase: tools for microRNA genomics. Nucleic Acids Res. 36(Database issue), D154-D158 (2008).
197. Hsu PW, Huang HD, Hsu SD et al. miRNAMap: genomic maps of microRNA genes and their target genes in mammalian genomes. Nucleic Acids Res. 34(Database issue), D135-D139 (2006).
198. Tam S, Tsao MS, Mcpherson JD. Optimization of miRNAseq data preprocessing. Brief Bioinform. doi:bbv019 [pii]10. 1093/bib/bbv019 (2015) (Epub ahead of print).
199. Capece V, Garcia Vizcaino JC, Vidal R et al. Oasis: online analysis of small RNA deep sequencing data. Bioinformatics doi:btv113 [pii]10. 1093/bioinformatics/btv113 (2015) (Epub ahead of print).
200. Gong J, Wu Y, Zhang X et al. Comprehensive analysis of human small RNA sequencing data provides insights into expression profiles and miRNA editing. RNA Biol. 11(11), 1375-1385 (2014).
201. Jang I, Chang H, Jun Y et al. miRseqViewer: multi-panel visualization of sequence, structure and expression for analysis of microRNA sequencing data. Bioinformatics 31(4), 596-598 (2015).
202. Gunaratne PH, Coarfa C, Soibam B, Tandon A. miRNA data analysis: next-gen sequencing. Methods Mol. Biol. 822, 273-288 (2012).
203. Yang JH, Qu LH. DeepBase: annotation and discovery of microRNAs and other noncoding RNAs from deepsequencing data. Methods Mol. Biol. 822 233-248 (2012).
204. Muller S, Raulefs S, Bruns P et al. Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer. Mol. Cancer 14(1), 94 (2015).
205. Chang YY, Kuo WH, Hung JH et al. Deregulated microRNAs in triple-negative breast cancer revealed by deep sequencing. Mol. Cancer 14(1), 36 (2015).
206. 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. 141(5), 672-675 (2008).
207. Chim SS, Shing TK, Hung EC et al. Detection and characterization of placental microRNAs in maternal plasma. Clin. Chem. 54(3), 482-490 (2008).
208. Mitchell PS, Parkin RK, Kroh EM et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl Acad. Sci. USA 105(30), 10513-10518 (2008).
209. Witwer KW. Circulating microRNA biomarker studies: pitfalls and potential solutions. Clin. Chem. 61(1), 56-63 (2015).
210. Gilad S, Lithwick-Yanai G, Barshack I et al. Classification of the four main types of lung cancer using a microRNA-based diagnostic assay. J. Mol. Diagn. 14(5), 510-517 (2012).
211. Amur S, Lavange L, Zineh I, Buckman-Garner S, Woodcock J. Biomarker Qualification: Toward a multi-stakeholder framework for biomarker development, regulatory acceptance, and utilization. Clin. Pharmacol. Ther. doi:10. 1002/cpt. 136 (2015) (Epub ahead of print).
212. Lorincz A. Scratching the surface of tomorrow's diagnostics: the Editor-in-Chief 's opinion at the 15th year of Expert Review of Molecular Diagnostics. Expert Rev. Mol. Diagn. 15(1), 5-8 (2015).
213. Gehlenborg N, O'donoghue SI, Baliga NS et al. Visualization of omics data for systems biology. Nat Methods 7(3 Suppl.), S56-S68 (2010).
214. Chen R, Mias GI, Li-Pook-Than J et al. Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell 148(6), 1293-1307 (2012).
215. Oda Y, Nakajima M, Tsuneyama K et al. Retinoid X receptor alpha in human liver is regulated by miR-34a. Biochem. Pharmacol. 90(2), 179-187 (2014).
216. Nakano M, Fukushima Y, Yokota S et al. CYP2A7 pseudogene transcript affects CYP2A6 expression in human liver by acting as a decoy for miR-126. Drug Metab. Dispos. 43(5), 703-712 (2015).
217. Coda DM, Lingua MF, Morena D et al. Smyd1 and G6Pd modulation are critical events for Mir-206-mediated differentiation of rhabdomyosarcoma. Cell Cycle doi:10. 1080 /15384101. 2015. 1005993 (2015) (Epub ahead of print).
218. Sun C, Huang F, Liu X et al. miR-21 regulates triglyceride and cholesterol metabolism in non-alcoholic fatty liver disease by targeting HMGCR. Int. J. Mol. Med. 35(3), 847-853 (2015).
219. Dong X, Liu H, Chen F, Li D, Zhao Y. MiR-214 promotes the alcohol-induced oxidative stress via down-regulation of glutathione reductase and cytochrome P450 oxidoreductase in liver cells. Alcohol Clin. Exp. Res. 38(1), 68-77 (2014).
220. Gotanda K, Hirota T, Matsumoto N, Ieiri I. MicroRNA-433 negatively regulates the expression of thymidylate synthase (TYMS) responsible for 5-fluorouracil sensitivity in HeLa cells. BMC Cancer 13 369 (2013).
221. Cui M, Xiao Z, Sun B et al. Involvement of cholesterol in hepatitis B virus X protein-induced abnormal lipid metabolism of hepatoma cells via up-regulating miR-205-targeted ACSL4. Biochem. Biophys. Res. Commun. 445(3), 651-655 (2014).
222. Endo Y, Yamashita H, Takahashi S et al. Immunohistochemical determination of the miR-1290 target arylamine N-acetyltransferase 1 (NAT1) as a prognostic biomarker in breast cancer. BMC Cancer 14 990 (2014).
223. Ma W, Ding H, Gong X et al. Methyl protodioscin increases ABCA1 expression and cholesterol efflux while inhibiting gene expressions for synthesis of cholesterol and triglycerides by suppressing SREBP transcription and microRNA 33a/b levels. Atherosclerosis 239(2), 566-570 (2015).
224. Meiler S, Baumer Y, Toulmin E, Seng K, Boisvert WA. MicroRNA 302a is a novel modulator of cholesterol homeostasis and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 35(2), 323-331 (2015).
225. Lv YC, Tang YY, Peng J et al. MicroRNA-19b promotes macrophage cholesterol accumulation and aortic atherosclerosis by targeting ATP-binding cassette transporter A1. Atherosclerosis 236(1), 215-226 (2014).
226. Zhao R, Feng J, He G. miR-613 regulates cholesterol efflux by targeting LXRalpha and ABCA1 in PPARgamma activated THP-1 macrophages. Biochem. Biophys. Res. Commun. 448(3), 329-334 (2014).
227. Zhang M, Wu JF, Chen WJ et al. MicroRNA-27a/b regulates cellular cholesterol efflux, influx and esterification/hydrolysis in THP-1 macrophages. Atherosclerosis 234(1), 54-64 (2014).
228. Ma J, Wang T, Guo R et al. Involvement of miR-133a and miR-326 in ADM resistance of HepG2 through modulating expression of ABCC1. J. Drug Target. doi:10. 3109/106118 6X. 2015. 1015536 1-6 (2015) (Epub ahead of print).
229. Pan YZ, Zhou A, Hu Z, Yu AM. Small nucleolar RNAderived microRNA hsa-miR-1291 modulates cellular drug disposition through direct targeting of ABC transporter ABCC1. Drug Metab. Dispos. 41(10), 1744-1751 (2013).
230. Markova SM, Kroetz DL. ABCC4 is regulated by microRNA-124a and microRNA-506. Biochem. Pharmacol. 87(3), 515-522 (2014).
231. Shi L, Wang Z, Sun G, Wan Y, Guo J, Fu X. miR-145 inhibits migration and invasion of glioma stem cells by targeting ABCG2. Neuromol. Med. 16(2), 517-528 (2014).
232. Song L, Li Y, Li W, Wu S, Li Z. miR-495 enhances the sensitivity of non-small cell lung cancer cells to platinum by modulation of copper-transporting P-type adenosine triphosphatase A (ATP7A). J. Cell. Biochem. 115(7), 1234-1242 (2014).
233. Kim S, Rhee JK, Yoo HJ et al. Bioinformatic and metabolomic analysis reveals miR-155 regulates thiamine level in breast cancer. Cancer Lett. 357(2), 488-497 (2015).
234. Zhang B, Liu T, Wu T, Wang Z, Rao Z, Gao J. microRNA-137 functions as a tumor suppressor in human non-small cell lung cancer by targeting SLC22A18. Int. J. Biol. Macromol. 74, 111-118 (2015).
235. Dai DW, Lu Q, Wang LX et al. Decreased miR-106a inhibits glioma cell glucose uptake and proliferation by targeting SLC2A3 in GBM. BMC Cancer 13 478 (2013).
236. Drayton RM, Dudziec E, Peter S et al. Reduced expression of miRNA-27a modulates cisplatin resistance in bladder cancer by targeting the cystine/glutamate exchanger SLC7A11. Clin. Cancer Res. 20(7), 1990-2000 (2014).
237. Zhu H, Wu H, Liu X et al. Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem. Pharmacol. 76(5), 582-588 (2008).
238. Zhao XH, Yang L, Hu JG. Down-regulation of miR-27a might inhibit proliferation and drug resistance of gastric cancer cells. J. Exp. Clin. Cancer Res. 30, 55 (2011).
239. Harvey H, Piskareva O, Creevey L et al. Modulation of chemotherapeutic drug resistance in neuroblastoma SK-NAS cells by the neural apoptosis inhibitory protein and miR-520f. Int. J. Cancer 136(7), 1579-1588 (2015).