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Review

Epigenetic regulation of drug transporter expression in human tissues

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Pages 19-30 | Received 30 May 2016, Accepted 24 Aug 2016, Published online: 07 Sep 2016

References

  • Sissung TM, Troutman SM, Campbell TJ, et al. Transporter pharmacogenetics: transporter polymorphisms affect normal physiology, diseases, and pharmacotherapy. Discov Med. 2012;13:19–34.
  • Bonder MJ, Kasela S, Kals M, et al. Genetic and epigenetic regulation of gene expression in fetal and adult human livers. BMC Genomics. 2014;15:860.
  • Ivanov M, Kacevska M, Ingelman-Sundberg M. Epigenomics and interindividual differences in drug response. Clin Pharmacol Ther. 2012;92:727–736.
  • Ingelman-Sundberg M, Sim SC, Gomez A, et al. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther. 2007;116:496–526.
  • Wagner PD, Verma M, Srivastava S. Challenges for biomarkers in cancer detection. Ann NY Acad Sci. 2004;1022:9–16.
  • Robertson KD. DNA methylation and human disease. Nat Rev Genet. 2005;6:597–610.
  • Wilson AS, Power BE, Molloy PL. DNA hypomethylation and human diseases. Biochim Biophys Acta. 2007;1775:138–162.
  • Wu L-XX, Wen C-JJ, Li Y, et al. Interindividual epigenetic variation in ABCB1 promoter and its relationship with ABCB1 expression and function in healthy Chinese subjects. Br J Clin Pharmacol. 2015;80:1109–1121.
  • Efferth T, Futscher BW, Osieka R. 5-Azacytidine modulates the response of sensitive and multidrug-resistant K562 leukemic cells to cytostatic drugs. Blood Cells Mol Dis. 2001;27:637–648.
  • David GL, Yegnasubramanian S, Kumar A, et al. MDR1 promoter hypermethylation in MCF-7 human breast cancer cells: changes in chromatin structure induced by treatment with 5-Aza-cytidine. Cancer Biol Ther. 2004;3:540–548.
  • Takeda M, Mizokami A, Mamiya K, et al. The establishment of two paclitaxel-resistant prostate cancer cell lines and the mechanisms of paclitaxel resistance with two cell lines. Prostate. 2007;67:955–967.
  • Marguerite V, Beri-Dexheimer M, Ortiou S, et al. Cobalamin potentiates vinblastine cytotoxicity through downregulation of mdr-1 gene expression in HepG2 cells. Cell Physiol Biochem. 2007;20:967–761.
  • Reed K, Hembruff SL, Laberge ML, et al. Hypermethylation of the ABCB1 downstream gene promoter accompanies ABCB1 gene amplification and increased expression in docetaxel-resistant MCF-7 breast tumor cells. Epigenetics. 2008;3:270–280.
  • Reed K, Hembruff SL, Sprowl JA, et al. The temporal relationship between ABCB1 promoter hypomethylation, ABCB1 expression and acquisition of drug resistance. Pharmacogenomics J. 2010;10:489–504.
  • Shi C-JJ, Wang F, Ren M-FF, et al. Up-regulation of ABCB1/P-glycoprotein by escaping promoter hypermethylation indicates poor prognosis in hematologic malignancy patients with and without bone marrow transplantation. Leuk Res. 2011;35:73–79.
  • To KK, Zhan Z, Bates SE. Aberrant promoter methylation of the ABCG2 gene in renal carcinoma. Mol Cell Biol. 2006;26:8572–8585.
  • Turner JG, Gump JL, Zhang C, et al. ABCG2 expression, function, and promoter methylation in human multiple myeloma. Blood. 2006;108:3881–3889.
  • Nakano H, Nakamura Y, Soda H, et al. Methylation status of breast cancer resistance protein detected by methylation-specific polymerase chain reaction analysis is correlated inversely with its expression in drug-resistant lung cancer cells. Cancer. 2008;112:1122–1130.
  • Nakamichi N, Morii E, Ikeda J, et al. Synergistic effect of interleukin-6 and endoplasmic reticulum stress inducers on the high level of ABCG2 expression in plasma cells. Lab Invest. 2009;89:327–336.
  • Bram EE, Stark M, Raz S, et al. Chemotherapeutic drug-induced ABCG2 promoter demethylation as a novel mechanism of acquired multidrug resistance. Neoplasia. 2009;11:1359–1370.
  • Porro A, Iraci N, Soverini S, et al. c-MYC oncoprotein dictates transcriptional profiles of ATP-binding cassette transporter genes in chronic myelogenous leukemia CD34+ hematopoietic progenitor cells. Mol Cancer Res. 2011;9:1054–1066.
  • Schaeffeler E, Hellerbrand C, Nies AT, et al. DNA methylation is associated with downregulation of the organic cation transporter OCT1 (SLC22A1) in human hepatocellular carcinoma. Genome Med. 2011;3:82.
  • Lin R, Li X, Li J, et al. Long-term cisplatin exposure promotes methylation of the OCT1 gene in human esophageal cancer cells. Dig Dis Sci. 2013;58:694–698.
  • Aoki M, Terada T, Kajiwara M, et al. Kidney-specific expression of human organic cation transporter 2 (OCT2/SLC22A2) is regulated by DNA methylation. Am J Physiol Renal Physiol. 2008;295:F165–F170.
  • Ikehata M, Ueda K, Iwakawa S. Different involvement of DNA methylation and histone deacetylation in the expression of solute-carrier transporters in 4 colon cancer cell lines. Biol Pharm Bull. 2012;35:301–307.
  • Chen L, Hong C, Chen EC, et al. Genetic and epigenetic regulation of the organic cation transporter 3, SLC22A3. Pharmacogenomics J. 2013;13:110–120.
  • Qu Q, Qu J, Zhan M, et al. Different involvement of promoter methylation in the expression of organic cation/carnitine transporter 2 (OCTN2) in cancer cell lines. PLoS ONE. 2013;8:e76474.
  • Jin L, Kikuchi R, Saji T, et al. Regulation of tissue-specific expression of renal organic anion transporters by hepatocyte nuclear factor 1 α/β and DNA methylation. J Pharmacol Exp Ther. 2012;340:648–655.
  • Kikuchi R, Kusuhara H, Hattori N, et al. Regulation of the expression of human organic anion transporter 3 by hepatocyte nuclear factor 1alpha/beta and DNA methylation. Mol Pharmacol. 2006;70:887–896.
  • Imai S, Kikuchi R, Kusuhara H, et al. DNA methylation and histone modification profiles of mouse organic anion transporting polypeptides. Drug Metab Dispos. 2013;41:72–78.
  • Imai S, Kikuchi R, Tsuruya Y, et al. Epigenetic regulation of organic anion transporting polypeptide 1B3 in cancer cell lines. Pharm Res. 2013;30:2880–2890.
  • Kim RB. Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metab Rev. 2002;34:47–54.
  • Sharom FJ. The P-glycoprotein multidrug transporter. Essays Biochem. 2011;50:161–178.
  • Ueda K, Clark DP, Chen CJ, et al. The human multidrug resistance (mdr1) gene. cDNA cloning and transcription initiation. J Biol Chem. 1987;262:505–508.
  • Huff LM, Wang Z, Iglesias A, et al. Aberrant transcription from an unrelated promoter can result in MDR-1 expression following drug selection in vitro and in relapsed lymphoma samples. Cancer Res. 2005;65:11694–11703.
  • Raguz S, Randle RA, Sharpe ER, et al. Production of P-glycoprotein from the MDR1 upstream promoter is insufficient to affect the response to first-line chemotherapy in advanced breast cancer. Int J Cancer. 2008;122:1058–1067.
  • Mealey KL. ABCG2 transporter: therapeutic and physiologic implications in veterinary species. J Vet Pharmacol Ther. 2012;35:105–112.
  • Hilgendorf C, Ahlin G, Seithel A, et al. Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines. Drug Metab Dispos. 2007;35:1333–1340.
  • Kunze A, Huwyler J, Camenisch G, et al. Prediction of organic anion-transporting polypeptide 1B1- and 1B3-mediated hepatic uptake of statins based on transporter protein expression and activity data. Drug Metab Dispos. 2014;42:1514–1521.
  • Treiber A, Schneiter R, Häusler S, et al. Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos. 2007;35:1400–1407.
  • Sato T, Yamaguchi H, Kogawa T, et al. Organic anion transporting polypeptides 1B1 and 1B3 play an important role in uremic toxin handling and drug-uremic toxin interactions in the liver. J Pharm Pharm Sci. 2014;17:475–484.
  • Nagai M, Furihata T, Matsumoto S, et al. Identification of a new organic anion transporting polypeptide 1B3 mRNA isoform primarily expressed in human cancerous tissues and cells. Biochem Biophys Res Commun. 2012;418:818–823.
  • Feng Q, Zhang Y. The MeCP1 complex represses transcription through preferential binding, remodeling, and deacetylating methylated nucleosomes. Genes Dev. 2001;15:827–832.
  • Ye J, Liu Q, Wang C, et al. Inhibitory effect of JBP485 on renal excretion of acyclovir by the inhibition of OAT1 and OAT3. Eur J Pharm Sci. 2012;47:341–346.
  • Ueo H, Motohashi H, Katsura T, et al. Human organic anion transporter hOAT3 is a potent transporter of cephalosporin antibiotics, in comparison with hOAT1. Biochem Pharmacol. 2005;70:1104–1113.
  • Tahara H, Kusuhara H, Endou H, et al. A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters. J Pharmacol Exp Ther. 2005;315:337–345.
  • More SS, Li S, Yee SW, et al. Organic cation transporters modulate the uptake and cytotoxicity of picoplatin, a third-generation platinum analogue. Mol Cancer Ther. 2010;9:1058–1069.
  • Nies AT, Koepsell H, Winter S, et al. Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology. 2009;50:1227–1240.
  • Kimura N, Okuda M, Inui K. Metformin transport by renal basolateral organic cation transporter hOCT2. Pharm Res. 2005;22:255–259.
  • Backs J, Olson EN. Control of cardiac growth by histone acetylation/deacetylation. Circ Res. 2006;98:15–24.
  • Lobera M, Madauss KP, Pohlhaus DT, et al. Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group. Nat Chem Biol. 2013;9:319–325.
  • Xiao JJ, Huang Y, Dai Z, et al. Chemoresistance to depsipeptide FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,22-pentanone] is mediated by reversible MDR1 induction in human cancer cell lines. J Pharmacol Exp Ther. 2005;314:467–475.
  • Baker EK, Johnstone RW, Zalcberg JR, et al. Epigenetic changes to the MDR1 locus in response to chemotherapeutic drugs. Oncogene. 2005;24:8061–8075.
  • Chen KG, Wang YC, Schaner ME, et al. Genetic and epigenetic modeling of the origins of multidrug-resistant cells in a human sarcoma cell line. Cancer Res. 2005;65:9388–9397.
  • Yatouji S, El-Khoury V, Trentesaux C, et al. Differential modulation of nuclear texture, histone acetylation, and MDR1 gene expression in human drug-sensitive and -resistant OV1 cell lines. Int J Oncol. 2007;30:1003–1009.
  • El-Khoury V, Breuzard G, Fourré N, et al. The histone deacetylase inhibitor trichostatin A downregulates human MDR1 (ABCB1) gene expression by a transcription-dependent mechanism in a drug-resistant small cell lung carcinoma cell line model. Br J Cancer. 2007;97:562–573.
  • Hirota T, Takane H, Higuchi S, et al. Epigenetic regulation of genes encoding drug-metabolizing enzymes and transporters; DNA methylation and other mechanisms. Curr Drug Metab. 2008;9:34–38.
  • Lee T-B-B, Park J-H-H, Min Y-D-D, et al. Epigenetic mechanisms involved in differential MDR1 mRNA expression between gastric and colon cancer cell lines and rationales for clinical chemotherapy. BMC Gastroenterol. 2008;8:33.
  • Kim S-NN, Kim NH, Lee W, et al. Histone deacetylase inhibitor induction of P-glycoprotein transcription requires both histone deacetylase 1 dissociation and recruitment of CAAT/enhancer binding protein beta and pCAF to the promoter region. Mol Cancer Res. 2009;7:735–744.
  • Hauswald S, Duque-Afonso J, Wagner MM, et al. Histone deacetylase inhibitors induce a very broad, pleiotropic anticancer drug resistance phenotype in acute myeloid leukemia cells by modulation of multiple ABC transporter genes. Clin Cancer Res. 2009;15:3705–3715.
  • Jin W, Liu Y, Xu SG, et al. UHRF1 inhibits MDR1 gene transcription and sensitizes breast cancer cells to anticancer drugs. Breast Cancer Res Treat. 2010;124:39–48.
  • Xu Y, Jiang Z, Yin P, et al. Role for class I histone deacetylases in multidrug resistance. Exp Cell Res. 2012;318:177–186.
  • Toth M, Boros IM, Balint E. Elevated level of lysine 9-acetylated histone H3 at the MDR1 promoter in multidrug-resistant cells. Cancer Sci. 2012;103:659–669.
  • Kim H, Kim S-NN, Park Y-SS, et al. HDAC inhibitors downregulate MRP2 expression in multidrug resistant cancer cells: implication for chemosensitization. Int J Oncol. 2011;38:807–127.
  • To KK, Polgar O, Huff LM, et al. Histone modifications at the ABCG2 promoter following treatment with histone deacetylase inhibitor mirror those in multidrug-resistant cells. Mol Cancer Res. 2008;6:151–164.
  • Zhou S-FF, Wang L-LL, Di YM, et al. Substrates and inhibitors of human multidrug resistance associated proteins and the implications in drug development. Curr Med Chem. 2008;15:1981–2039.
  • Huo H, Magro PG, Pietsch EC, et al. Histone methyltransferase MLL1 regulates MDR1 transcription and chemoresistance. Cancer Res. 2010;70:8726–8735.
  • Saito J, Hirota T, Kikunaga N, et al. Interindividual differences in placental expression of the SLC22A2 (OCT2) gene: relationship to epigenetic variations in the 5ʹ-upstream regulatory region. J Pharm Sci. 2011;100:3875–3883.
  • Sadakierska-Chudy A, Filip M. A comprehensive view of the epigenetic landscape. Part II: histone post-translational modification, nucleosome level, and chromatin regulation by ncRNAs. Neurotox Res. 2015;27:172–197.
  • Lv Y-CC, Tang Y-YY, Peng J, et al. MicroRNA-19b promotes macrophage cholesterol accumulation and aortic atherosclerosis by targeting ATP-binding cassette transporter A1. Atherosclerosis. 2014;236:215–226.
  • Goedeke L, Rotllan N, Ramírez CM, et al. miR-27b inhibits LDLR and ABCA1 expression but does not influence plasma and hepatic lipid levels in mice. Atherosclerosis. 2015;243:499–509.
  • Jan A, Karasinska JM, Kang MH, et al. Direct intracerebral delivery of a miR-33 antisense oligonucleotide into mouse brain increases brain ABCA1 expression. [Corrected]. Neurosci Lett. 2015;598:66–72.
  • Rayner KJ, Esau CC, Hussain FN, et al. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature. 2011;478:404–407.
  • Zhang N, Lei J, Lei H, et al. MicroRNA-101 overexpression by IL-6 and TNF-α inhibits cholesterol efflux by suppressing ATP-binding cassette transporter A1 expression. Exp Cell Res. 2015;336:33–42.
  • De Aguiar Vallim TQ, Tarling EJ, Kim T, et al. MicroRNA-144 regulates hepatic ATP binding cassette transporter A1 and plasma high-density lipoprotein after activation of the nuclear receptor farnesoid X receptor. Circ Res. 2013;112:1602–1612.
  • Goedeke L, Rotllan N, Canfrán-Duque A, et al. MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels. Nat Med. 2015;21:1280–1289.
  • 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. 2008;76:582–588.
  • Li Z, Hu S, Wang J, et al. MiR-27a modulates MDR1/P-glycoprotein expression by targeting HIPK2 in human ovarian cancer cells. Gynecol Oncol. 2010;119:125–130.
  • Feng -D-D-D, 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. 2011;15:2164–2175.
  • Zhang H, Li M, Han Y, et al. Down-regulation of miR-27a might reverse multidrug resistance of esophageal squamous cell carcinoma. Dig Dis Sci. 2010;55:2545–2551.
  • Chen Z, Ma T, Huang C, et al. MiR-27a modulates the MDR1/P-glycoprotein expression by inhibiting FZD7/β-catenin pathway in hepatocellular carcinoma cells. Cell Signal. 2013;25:2693–2701.
  • Long Q-Z-Z, Du Y-F-F, Liu X-G-G, et al. miR-124 represses FZD5 to attenuate P-glycoprotein-mediated chemo-resistance in renal cell carcinoma. Tumour Biol. 2015;36:7017–7026.
  • Yang L, Li N, Wang H, et al. Altered microRNA expression in cisplatin-resistant ovarian cancer cells and upregulation of miR-130a associated with MDR1/P-glycoprotein-mediated drug resistance. Oncol Rep. 2012;28:592–600.
  • Takwi AA, Wang Y-MM, Wu J, et al. miR-137 regulates the constitutive androstane receptor and modulates doxorubicin sensitivity in parental and doxorubicin-resistant neuroblastoma cells. Oncogene. 2014;33:3717–3729.
  • Zhao X, Yang L, Hu J, et al. miR-138 might reverse multidrug resistance of leukemia cells. Leuk Res. 2010;34:1078–1082.
  • Ikemura K, Yamamoto M, Miyazaki S, et al. MicroRNA-145 post-transcriptionally regulates the expression and function of P-glycoprotein in intestinal epithelial cells. Mol Pharmacol. 2013;83:399–405.
  • Chen J, Tian W, Cai H, et al. Down-regulation of microRNA-200c is associated with drug resistance in human breast cancer. Med Oncol. 2012;29:2527–2534.
  • Sui H, Cai GX, Pan SF, et al. miR200c attenuates P-gp-mediated MDR and metastasis by targeting JNK2/c-Jun signaling pathway in colorectal cancer. Mol Cancer Ther. 2014;13:3137–3151.
  • Yang T, Zheng Z-M-M, Li X-N-N, et al. MiR-223 modulates multidrug resistance via downregulation of ABCB1 in hepatocellular carcinoma cells. Exp Biol Med (Maywood). 2013;238:1024–1032.
  • Bao L, Hazari S, Mehra S, et al. Increased expression of P-glycoprotein and doxorubicin chemoresistance of metastatic breast cancer is regulated by miR-298. Am J Pathol. 2012;180:2490–2503.
  • Xu Y, Ohms SJ, Li Z, et al. Changes in the expression of miR-381 and miR-495 are inversely associated with the expression of the MDR1 gene and development of multi-drug resistance. PLoS ONE. 2013;8:e82062.
  • 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. 2008;7:2152–2159.
  • Shang Y, Zhang Z, Liu Z, et al. miR-508-5p regulates multidrug resistance of gastric cancer by targeting ABCB1 and ZNRD1. Oncogene. 2014;33:3267–3276.
  • Pogribny IP, Filkowski JN, Tryndyak VP, et al. Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. Int J Cancer. 2010;127:1785–1794.
  • Liu H, Wu X, Huang J, et al. miR-7 modulates chemoresistance of small cell lung cancer by repressing MRP1/ABCC1. Int J Exp Pathol. 2015;96:240–247.
  • 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. 2015;23:519–524.
  • Lu L, Ju F, Zhao H, et al. MicroRNA-134 modulates resistance to doxorubicin in human breast cancer cells by downregulating ABCC1. Biotechnol Lett. 2015;37:2387–2394.
  • Liang Z, Wu H, Xia J, et al. Involvement of miR-326 in chemotherapy resistance of breast cancer through modulating expression of multidrug resistance-associated protein 1. Biochem Pharmacol. 2010;79:817–824.
  • Pan Y-Z-Z, Zhou A, Hu Z, et al. Small nucleolar RNA-derived microRNA hsa-miR-1291 modulates cellular drug disposition through direct targeting of ABC transporter ABCC1. Drug Metab Dispos. 2013;41:1744–1751.
  • Xu K, Liang X, Shen K, et al. miR-297 modulates multidrug resistance in human colorectal carcinoma by down-regulating MRP-2. Biochem J. 2012;446:291–300.
  • Haenisch S, Laechelt S, Bruckmueller H, et al. Down-regulation of ATP-binding cassette C2 protein expression in HepG2 cells after rifampicin treatment is mediated by microRNA-379. Mol Pharmacol. 2011;80:314–320.
  • Shen W-WW, Zeng Z, Zhu W-XX, et al. MiR-142-3p functions as a tumor suppressor by targeting CD133, ABCG2, and Lgr5 in colon cancer cells. J Mol Med. 2013;91:989–10001.
  • Jiao X, Zhao L, Ma M, et al. MiR-181a enhances drug sensitivity in mitoxantone-resistant breast cancer cells by targeting breast cancer resistance protein (BCRP/ABCG2). Breast Cancer Res Treat. 2013;139:717–730.
  • Cheng W, Liu T, Wan X, et al. MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells. FEBS J. 2012;279:2047–2059.
  • Turrini E, Haenisch S, Laechelt S, et al. MicroRNA profiling in K-562 cells under imatinib treatment: influence of miR-212 and miR-328 on ABCG2 expression. Pharmacogenet Genomics. 2012;22:198–205.
  • Pan Y-ZZ, Morris ME, Yu A-MM. MicroRNA-328 negatively regulates the expression of breast cancer resistance protein (BCRP/ABCG2) in human cancer cells. Mol Pharmacol. 2009;75:1374–1379.
  • Li X, Pan YZ, Seigel GM, et al. Breast cancer resistance protein BCRP/ABCG2 regulatory microRNAs (hsa-miR-328, −519c and −520h) and their differential expression in stem-like ABCG2+ cancer cells. Biochem Pharmacol. 2011;81:783–792.
  • Ma M-TT, He M, Wang Y, et al. MiR-487a resensitizes mitoxantrone (MX)-resistant breast cancer cells (MCF-7/MX) to MX by targeting breast cancer resistance protein (BCRP/ABCG2). Cancer Lett. 2013;339:107–115.
  • To KK, Zhan Z, Litman T, et al. Regulation of ABCG2 expression at the 3ʹ untranslated region of its mRNA through modulation of transcript stability and protein translation by a putative microRNA in the S1 colon cancer cell line. Mol Cell Biol. 2008;28:5147–5161.
  • Padmanabhan R, Chen KG, Gillet J-P-P, et al. Regulation and expression of the ATP-binding cassette transporter ABCG2 in human embryonic stem cells. Stem Cells. 2012;30:2175–2187.
  • To KK, Leung WW, Ng SS. Exploiting a novel miR-519c-HuR-ABCG2 regulatory pathway to overcome chemoresistance in colorectal cancer. Exp Cell Res. 2015;338:222–231.
  • Oram JF, Lawn RM. ABCA1. The gatekeeper for eliminating excess tissue cholesterol. J Lipid Res. 2001;42:1173–1179.
  • Lv YC, Yin K, Fu YC, et al. Posttranscriptional regulation of ATP-binding cassette transporter A1 in lipid metabolism. DNA Cell Biol. 2013;32:348–358.
  • Oram JF, Heinecke JW. ATP-binding cassette transporter A1: a cell cholesterol exporter that protects against cardiovascular disease. Physiol Rev. 2005;85:1343–1372.
  • Rikke-Schmidt R, Nordestgaard BGG, Jensen GB, et al. Genetic variation in ABC transporter A1 contributes to HDL cholesterol in the general population. J Clin Invest. 2004;114:1343–1353.
  • Wang D, Sadée W. Searching for polymorphisms that affect gene expression and mRNA processing: example ABCB1 (MDR1). Aaps J. 2006;8:E515–201.
  • Kimchi-Sarfaty C, Oh JM, Kim I-W-W, et al. A “silent” polymorphism in the MDR1 gene changes substrate specificity. Science. 2007;315:525–528.
  • Bruhn O, Drerup K, Kaehler M, et al. Length variants of the ABCB1 3′-UTR and loss of miRNA binding sites: possible consequences in regulation and pharmacotherapy resistance. Pharmacogenomics. 2016;17:327–340.
  • Liu H, Wu X, Huang J, et al. miR-7 modulates chemoresistance of small cell lung cancer by repressing MRP1/ABCC1. Int J Exp Pathol. 2015;96:240–247.
  • Ripperger A, Benndorf RA. The C421A (Q141K) polymorphism enhances the 3ʹ-untranslated region (3ʹ-UTR)-dependent regulation of ATP-binding cassette transporter ABCG2. Biochem Pharmacol. 2016;104:139–147.
  • Saito J, Hirota T, Furuta S, . Association between DNA methylation in the miR-328 5’-Flanking region and inter-individual differences in miR-328 and BCRP expression in human placenta. PLoS ONE. 2013;8:e729061.
  • Wong AH, Gottesman II, Petronis A. Phenotypic differences in genetically identical organisms: the epigenetic perspective. Hum Mol Genet. 2005;14 Spec No 1:R11–R18.
  • Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105:10513–10518.
  • Gilad S, Meiri E, Yogev Y, et al. Serum microRNAs are promising novel biomarkers. PLoS ONE. 2008;3:e3148.
  • Van Balkom BW, Eisele AS, Pegtel DM, et al. Quantitative and qualitative analysis of small RNAs in human endothelial cells and exosomes provides insights into localized RNA processing, degradation and sorting. J Extracell Vesicles. 2015;4:26760.
  • Breuninger S, Erl J, Knape C, et al. Quantitative analysis of liposomal heat shock protein 70 (Hsp70) in the blood of tumor patients using a novel LipHsp70 ELISA. J Clin Cell Immunol. 2014;5:264.
  • Gotanda K, Hirota T, Saito J, et al. Circulating intestine-derived exosomal miR-328 in plasma, a possible biomarker for estimating BCRP function in the human intestines. Sci Rep. 2016;6:32299.

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