Advertisement

MicroRNAs in Predicting Radiotherapy and Chemotherapy Response

  • Emily J. Noonan
  • Robert F. Place
  • Long-Cheng Li
Chapter

Abstract

Currently, many of the standard first line treatments for cancer consist of a combination of surgical removal, chemotherapy (CT), and radiotherapy (RT) of diseased tissue. During disease progression, tumor cells evolve and adapt to physiological states of resistance. Tumor biomarkers are proven to be useful in predicting response to CT, RT, and risk of recurrence. MicroRNAs (miRNAs) are small endogenous regulatory RNAs that are frequently dysregulated in cancer. A growing number of miRNAs are being identified in a variety of cancers with tumor suppressive and oncogenic functions. MiRNAs are also developing as a class of biomarkers that have been shown in both in vitro and in vivo studies to be useful in identifying malignant disease, classifying tumor subtypes, and as prognostic indicators. Additionally, circulating miRNAs are highly stable and detectable in tissue, urine, saliva, stool, sputum, and serum/plasma making them ideal candidates as cancer biomarkers. With these, a growing number of miRNAs have been identified as altering sensitivity to RT and CT. There is a number of previously established tumor suppressive and oncogenic miRNAs that function by regulating genes involved in cell cycle, apoptosis, multidrug resistance, and epithelial-mesenchymal transition. Use of miRNAs in predicting response to chemotherapeutics may give clinicians more accurate and/or sensitive methods to determine appropriate treatment choices.

Keywords

Acute Lymphocytic Leukemia Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia miRNA Expression NSCLC Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Adam L, Zhong M, Choi W, et al. MiR-200 expression regulates epithelial-to-mesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor receptor therapy. Clin Cancer Res. 2009;15:5060–72.PubMedCrossRefGoogle Scholar
  2. Ahmed N, Abubaker K, Findlay J, et al. Epithelial mesenchymal transition and cancer stem cell-like phenotypes facilitate chemoresistance in recurrent ovarian cancer. Curr Cancer Drug Targets. 2010;10:268–78.PubMedCrossRefGoogle Scholar
  3. Ahmed FE, Jeffries CD, Vos PW, et al. Diagnostic microRNA markers for screening sporadic human colon cancer and active ulcerative colitis in stool and tissue. Cancer Genomics Proteomics. 2009;6:281–95.PubMedGoogle Scholar
  4. Akao Y, Nakagawa Y, Naoe T. Let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biol Pharm Bull. 2006;29:903–6.PubMedCrossRefGoogle Scholar
  5. Akli S, Bui T, Wingate H, et al. Low-molecular-weight cyclin E can bypass letrozole-induced G1 arrest in human breast cancer cells and tumors. Clin Cancer Res. 2010;16:1179–90.PubMedCrossRefGoogle Scholar
  6. Arumugam T, Ramachandran V, Fournier KF, et al. Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res. 2009;69:5820–8.PubMedCrossRefGoogle Scholar
  7. Auner V, Sehouli J, Oskay-Oezcelik G, et al. Abc transporter gene expression in benign and malignant ovarian tissue. Gynecol Oncol. 2010;117:198–201.PubMedCrossRefGoogle Scholar
  8. Bai S, Nasser MW, Wang B, et al. MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem. 2009;284:32015–27.PubMedCrossRefGoogle Scholar
  9. Bandi N, Zbinden S, Gugger M, et al. MiR-15a and miR-16 are implicated in cell cycle regulation in a RB-dependent manner and are frequently deleted or down-regulated in non-small cell lung cancer. Cancer Res. 2009;69:5553–9.PubMedCrossRefGoogle Scholar
  10. Bandres E, Bitarte N, Arias F, et al. MicroRNA-451 regulates macrophage migration inhibitory factor production and proliferation of gastrointestinal cancer cells. Clin Cancer Res. 2009;15:2281–90.PubMedCrossRefGoogle Scholar
  11. Banwell CM, Singh R, Stewart PM, et al. Proliferative signalling by 1,25(OH)2D3 in prostate and breast cancer is suppressed by a mechanism involving histone deacetylation. Recent Results Cancer Res. 2003;164:83–98.PubMedGoogle Scholar
  12. Bentzen SM. Theragnostic imaging for radiation oncology: dose-painting by numbers. Lancet Oncol. 2005;6:112–7.PubMedCrossRefGoogle Scholar
  13. Bhat-Nakshatri P, Newton TR, Goulet R Jr, et al. NF-kappaB activation and interleukin 6 production in fibroblasts by estrogen receptor-negative breast cancer cell-derived interleukin 1alpha. Proc Natl Acad Sci USA. 1998;95:6971–6.PubMedCrossRefGoogle Scholar
  14. Blower PE, Verducci JS, Lin S, et al. MicroRNA expression profiles for the NCI-60 cancer cell panel. Mol Cancer Ther. 2007;6:1483–91.PubMedCrossRefGoogle Scholar
  15. Bonci D, Coppola V, Musumeci M, et al. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008;14:1271–7.PubMedCrossRefGoogle Scholar
  16. Borralho PM, Kren BT, Castro RE, et al. MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in hct116 human colorectal cancer cells. FEBS J. 2009;276:6689–700.PubMedCrossRefGoogle Scholar
  17. Bottoni A, Piccin D, Tagliati F, et al. MiR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol. 2005;204:280–5.PubMedCrossRefGoogle Scholar
  18. Bourguignon LY, Spevak CC, Wong G, et al. Hyaluronan-CD44 interaction with protein kinase c(epsilon) promotes oncogenic signaling by the stem cell marker nanog and the production of microRNA-21, leading to down-regulation of the tumor suppressor protein pdcd4, anti-apoptosis, and chemotherapy resistance in breast tumor cells. J Biol Chem. 2009;284:26533–46.PubMedCrossRefGoogle Scholar
  19. Braconi C, Valeri N, Gasparini P, et al. Hepatitis C virus proteins modulate microRNA expression and chemosensitivity in malignant hepatocytes. Clin Cancer Res. 2010;16:957–66.PubMedCrossRefGoogle Scholar
  20. Buckley PG, Alcock L, Bryan K, et al. Chromosomal and miRNA expression patterns reveal biologically distinct subgroups of 11q- neuroblastoma. Clin Cancer Res. 2010;16:2971–8.PubMedCrossRefGoogle Scholar
  21. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66.PubMedCrossRefGoogle Scholar
  22. Calin GA, Liu CG, Sevignani C, et al. MicroRNA profiling reveals distinct signatures in b cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA. 2004;101:11755–60.PubMedCrossRefGoogle Scholar
  23. Cammareri P, Scopelliti A, Todaro M, et al. Aurora-a is essential for the tumorigenic capacity and chemoresistance of colorectal cancer stem cells. Cancer Res. 2010;70:4655–65.PubMedCrossRefGoogle Scholar
  24. Camps C, Buffa FM, Colella S, et al. Hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res. 2008;14:1340–8.PubMedCrossRefGoogle Scholar
  25. Cardoso F, Van’t Veer L, Rutgers E, et al. Clinical application of the 70-gene profile: the mindact trial. J Clin Oncol. 2008;26:729–35.PubMedCrossRefGoogle Scholar
  26. Carmeliet P, Ferreira V, Breier G, et al. Abnormal blood vessel development and lethality in embryos lacking a single vegf allele. Nature. 1996;380:435–9.PubMedCrossRefGoogle Scholar
  27. Cascio S, D’Andrea A, Ferla R, et al. MiR-20b modulates vegf expression by targeting HIF-1 alpha and STAT3 in MCF-7 breast cancer cells. J Cell Physiol. 2010;224:242–9.PubMedGoogle Scholar
  28. 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;18:997–1006.PubMedCrossRefGoogle Scholar
  29. Chen G, Zhu W, Shi D, et al. MicroRNA-181a sensitizes human malignant glioma U87MG cells to radiation by targeting bcl-2. Oncol Rep. 2010;23:997–1003.PubMedGoogle Scholar
  30. Cho WC. MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol. 2009;42:1273–81.PubMedCrossRefGoogle Scholar
  31. Christoffersen NR, Shalgi R, Frankel LB, et al. P53-independent up-regulation of miR-34a during oncogene-induced senescence represses myc. Cell Death Differ. 2010;17:236–45.PubMedCrossRefGoogle Scholar
  32. Cimmino A, Calin GA, Fabbri M, et al. MiR-15 and miR-16 induce apoptosis by targeting bcl2. Proc Natl Acad Sci USA. 2005;102:13944–9.PubMedCrossRefGoogle Scholar
  33. Cobleigh MA, Tabesh B, Bitterman P, et al. Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes. Clin Cancer Res. 2005;11(24 Pt 1):8623–31.PubMedCrossRefGoogle Scholar
  34. Cochrane DR, Spoelstra NS, Howe EN, et al. MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. Mol Cancer Ther. 2009;8:1055–66.CrossRefGoogle Scholar
  35. Cohn DE, Fabbri M, Valeri N, et al. Comprehensive miRNA profiling of surgically staged endometrial cancer. Am J Obstet Gynecol. 2010;22:656.Google Scholar
  36. Coley HM. Mechanisms and strategies to overcome chemotherapy resistance in metastatic breast cancer. Cancer Treat Rev. 2008;34:378–90.PubMedCrossRefGoogle Scholar
  37. Coley HM. Overcoming multidrug resistance in cancer: clinical studies of p-glycoprotein inhibitors. Methods Mol Biol. 2010;596:341–58.PubMedCrossRefGoogle Scholar
  38. Connolly EC, Van Doorslaer K, Rogler LE, et al. Over-expression of miR-21 promotes an in vitro metastatic phenotype by targeting the tumor suppressor rhob. Mol Cancer Res. 2010;8:691–700.PubMedCrossRefGoogle Scholar
  39. Corsten MF, Miranda R, Kasmieh R, et al. MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered s-trail in human gliomas. Cancer Res. 2007;67:8994–9000.PubMedCrossRefGoogle Scholar
  40. Cosmopoulos K, Pegtel M, Hawkins J, et al. Comprehensive profiling of Epstein-Barr virus microRNAs in nasopharyngeal carcinoma. J Virol. 2009;83:2357–67.PubMedCrossRefGoogle Scholar
  41. Dallas NA, Xia L, Fan F, et al. Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition. Cancer Res. 2009;69:1951–7.PubMedCrossRefGoogle Scholar
  42. Debucquoy A, Roels S, Goethals L, et al. Double blind randomized Phase II study with radiation+5-fluorouracil+/-celecoxib for resectable rectal cancer. Radiother Oncol. 2009;93:273–8.PubMedCrossRefGoogle Scholar
  43. Di Fiore R, Santulli A, Ferrante RD, et al. Identification and expansion of human osteosarcoma-cancer-stem cells by long-term 3-aminobenzamide treatment. J Cell Physiol. 2009;219:301–13.PubMedCrossRefGoogle Scholar
  44. Di Leva G, Gasparini P, Piovan C, et al. MicroRNA cluster 221-222 and estrogen receptor {alpha} interactions in breast cancer. J Natl Cancer Inst. 2010;102:706–21.PubMedCrossRefGoogle Scholar
  45. Dong Q, Meng P, Wang T, et al. MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. PLoS One. 2010;5:e10147.PubMedCrossRefGoogle Scholar
  46. Duncan TJ, Al-Attar A, Rolland P, et al. Cytoplasmic p27 expression is an independent prognostic factor in ovarian cancer. Int J Gynecol Pathol. 2010;29:8–18.PubMedCrossRefGoogle Scholar
  47. Evans SM, Jenkins WT, Shapiro M, et al. Evaluation of the concept of “Hypoxic fraction” As a descriptor of tumor oxygenation status. Adv Exp Med Biol. 1997;411:215–25.PubMedGoogle Scholar
  48. Faderl S, Keating MJ, Do KA, et al. Expression profile of 11 proteins and their prognostic significance in patients with chronic lymphocytic leukemia (CLL). Leukemia. 2002;16:1045–52.PubMedCrossRefGoogle Scholar
  49. Felicetti F, Errico MC, Bottero L, et al. The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms. Cancer Res. 2008;68:2745–54.PubMedCrossRefGoogle Scholar
  50. Ferrandiz N, Caraballo JM, Albajar M, et al. P21(Cip1) confers resistance to imatinib in human chronic myeloid leukemia cells. Cancer Lett. 2010;292:133–9.PubMedCrossRefGoogle Scholar
  51. Flynt AS, Li N, Thatcher EJ, et al. Zebrafish miR-214 modulates Hedgehog signaling to specify muscle cell fate. Nat Genet. 2007;39:259–63.PubMedCrossRefGoogle Scholar
  52. Fornari F, Grameri L, Ferracin M, et al. MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene. 2008;27:5651–61.PubMedCrossRefGoogle Scholar
  53. Fornari F, Grameri L, Giovannini C, et al. MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res. 2009;69:5761–7.PubMedCrossRefGoogle Scholar
  54. Fujita Y, Kojima K, Hamada N, et al. Effects of miR-34a on cell growth and chemoresistance in prostate cancer PC3 cells. Biochem Biophys Res Commun. 2008;377:114–9.PubMedCrossRefGoogle Scholar
  55. Gal H, Pandi G, Kanner AA, et al. MiR-451 and imatinib mesylate inhibit tumor growth of glioblastoma stem cells. Biochem Biophys Res Commun. 2008;376:86–90.PubMedCrossRefGoogle Scholar
  56. Galardi S, Mercatelli N, Giorda E, et al. MiR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1. J Biol Chem. 2007;282:23716–24.PubMedCrossRefGoogle Scholar
  57. Garofalo M, Di Leva G, Romano G, et al. MiR-221 & 222 regulate trail resistance and enhance tumorigenicity through PTEN and TIMP3 down-regulation. Cancer Cell. 2009;16:498–509.PubMedCrossRefGoogle Scholar
  58. Gascoyne RD, Adomat SA, Krajewski S, et al. Prognostic significance of bcl-2 protein expression and bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin’s lymphoma. Blood. 1997;90:244–51.PubMedGoogle Scholar
  59. Gee HE, Camps C, Buffa FM, et al. Hsa-miR-210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer. Cancer. 2010;116:2148–58.PubMedGoogle Scholar
  60. Giaccia AJ. Hypoxic stress proteins: survival of the fittest. Semin Radiat Oncol. 1996;6:46–58.PubMedCrossRefGoogle Scholar
  61. Giannakakis A, Sandaltzopoulos R, Greshock J, et al. MiR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer. Cancer Biol Ther. 2008;7:255–64.PubMedCrossRefGoogle Scholar
  62. Gibbons DL, Lin W, Creighton CJ, et al. Contextual extracellular cues promote tumor cell emt and metastasis by regulating miR-200 family expression. Genes Dev. 2009;23:2140–51.PubMedCrossRefGoogle Scholar
  63. Giovannetti E, Funel N, Peters GJ, et al. MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. Cancer Res. 2010;70:4528–38.PubMedCrossRefGoogle Scholar
  64. Gironella M, Seux M, Xie MJ, et al. Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci USA. 2007;104:16170–5.PubMedCrossRefGoogle Scholar
  65. Gottardo F, Liu CG, Ferracin M, et al. Micro-RNA profiling in kidney and bladder cancers. Urol Oncol. 2007;25:387–92.PubMedGoogle Scholar
  66. Gregory PA, Bert AG, Paterson EL, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10:593–601.PubMedCrossRefGoogle Scholar
  67. Guled M, Lahti L, Lindholm PM, et al. CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma – a miRNA microarray analysis. Genes Chromosomes Cancer. 2009;48:615–23.PubMedCrossRefGoogle Scholar
  68. Guo Y, Chen Z, Zhang L, et al. Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Res. 2008;68:26–33.PubMedCrossRefGoogle Scholar
  69. Guo L, Liu Y, Bai Y, et al. Gene expression profiling of drug-resistant small cell lung cancer cells by combining microRNA and cdna expression analysis. Eur J Cancer. 2010;46:1692–702.PubMedCrossRefGoogle Scholar
  70. Haimeur A, Conseil G, Deeley RG, et al. The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation. Curr Drug Metab. 2004;5:21–53.PubMedCrossRefGoogle Scholar
  71. Hanke M, Hoefig K, Merz H, et al. A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol Oncol. 2010;28:655–61.PubMedGoogle Scholar
  72. He X, Duan C, Chen J, et al. Let-7a elevates p21(WAF1) levels by targeting of NIRF and suppresses the growth of A549 lung cancer cells. FEBS Lett. 2009;583:3501–7.PubMedCrossRefGoogle Scholar
  73. He L, He X, Lim LP, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447:1130–4.PubMedCrossRefGoogle Scholar
  74. Hermine O, Haioun C, Lepage E, et al. Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin’s lymphoma. Groupe d’etude des lymphomes de l’adulte (gela). Blood. 1996;87:265–72.PubMedGoogle Scholar
  75. Honoki K. Do stem-like cells play a role in drug resistance of sarcomas? Expert Rev cancer Ther. 2010;10:261–70.CrossRefGoogle Scholar
  76. Horton JK, Halle J, Ferraro M, et al. Radiosensitization of chemotherapy-refractory, locally advanced or locally recurrent breast cancer with trastuzumab: a Phase II trial. Int J Radiat Oncol Biol Phys. 2010;76:998–1004.PubMedCrossRefGoogle Scholar
  77. 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. 2010b;28:1721–6.PubMedCrossRefGoogle Scholar
  78. Hu H, Li Y, Gu J, et al. Sense oligonucleotide against miR-21 inhibits migration and induces apoptosis in leukemic K562 cells. Leuk Lymphoma. 2010a;51:694–701.PubMedCrossRefGoogle Scholar
  79. Huang Q, Gumireddy K, Schrier M, et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol. 2008;10:202–10.PubMedCrossRefGoogle Scholar
  80. 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. 2010;5:e10630.PubMedCrossRefGoogle Scholar
  81. Inoue S, Mai A, Dyer MJ, et al. Inhibition of histone deacetylase class I but not class II is critical for the sensitization of leukemic cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. Cancer Res. 2006;66:6785–92.PubMedCrossRefGoogle Scholar
  82. Iorio MV, Casalini P, Piovan C, et al. MicroRNA-205 regulates HER3 in human breast cancer. Cancer Res. 2009;69:2195–200.PubMedCrossRefGoogle Scholar
  83. Jackson C, Cunningham D. A retrospective on the inhibition of epidermal growth factor receptor as a therapeutic strategy for patients with relapsed metastatic colorectal cancer: impact on treatment of today’s patients. Clin Colorectal Cancer. 2007;7(Suppl 1):S8–S15.PubMedCrossRefGoogle Scholar
  84. Jay C, Nemunaitis J, Chen P, et al. MiRNA profiling for diagnosis and prognosis of human cancer. DNA Cell Biol. 2007;26:293–300.PubMedCrossRefGoogle Scholar
  85. Ji Q, Hao X, Zhang M, et al. MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS One. 2009;4:e6816.PubMedCrossRefGoogle Scholar
  86. Jiang X, Gwye Y, Russell D, et al. CD133 expression in chemo-resistant ewing sarcoma cells. BMC Cancer. 2010;10:116.PubMedCrossRefGoogle Scholar
  87. Johansson M, Persson JL. Cancer therapy: targeting cell cycle regulators. Anticancer Agents Med Chem. 2008;8:723–31.PubMedGoogle Scholar
  88. Johnson SM, Grosshans H, Shingara J, et al. Ras is regulated by the let-7 microRNA family. Cell. 2005;120:635–47.PubMedCrossRefGoogle Scholar
  89. Jun HJ, Kim YM, Park SY, et al. Modulation of ionizing radiation-induced G2 arrest by cyclooxygenase-2 and its inhibitor celecoxib. Int J Radiat Oncol Biol Phys. 2009;75:225–34.PubMedCrossRefGoogle Scholar
  90. Kang MR, Lee K, Kang JS, et al. KBH-A42, a histone deacetylase inhibitor, inhibits the growth of doxorubicin-resistant leukemia cells expressing p-glycoprotein. Oncol Rep. 2010;23:801–9.PubMedGoogle Scholar
  91. Katada T, Ishiguro H, Kuwabara Y, et al. MicroRNA expression profile in undifferentiated gastric cancer. Int J Oncol. 2009;34:537–42.PubMedGoogle Scholar
  92. Kent OA, Mullendore M, Wentzel EA, et al. A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells. Cancer Biol Ther. 2009;8:2013–24.PubMedCrossRefGoogle Scholar
  93. Kinsella TJ. Coordination of DNA mismatch repair and base excision repair processing of chemotherapy and radiation damage for targeting resistant cancers. Clin Cancer Res. 2009;15:1853–9.PubMedCrossRefGoogle Scholar
  94. Knauer M, Mook S, Rutgers EJ, et al. The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer. Breast Cancer Res Treat. 2010;120:655–61.PubMedCrossRefGoogle Scholar
  95. Kong D, Li Y, Wang Z, et al. MiR-200 regulates PDGF-D-mediated epithelial-mesenchymal transition, adhesion, and invasion of prostate cancer cells. Stem Cells. 2009;27:1712–21.PubMedCrossRefGoogle Scholar
  96. Koong AC, Chen EY, Giaccia AJ. Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues. Cancer Res. 1994;54:1425–30.PubMedGoogle Scholar
  97. Kotani A, Ha D, Hsieh J, et al. MiR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221. Blood. 2009;114:4169–78.PubMedCrossRefGoogle Scholar
  98. 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;7:2152–9.PubMedCrossRefGoogle Scholar
  99. Krause M, Gurtner K, Deuse Y, et al. Heterogeneity of tumour response to combined radiotherapy and egfr inhibitors: differences between antibodies and tk inhibitors. Int J Radiat Biol. 2009;85:943–54.PubMedCrossRefGoogle Scholar
  100. Kulshreshtha R, Ferracin M, Wojcik SE, et al. A microRNA signature of hypoxia. Mol Cell Biol. 2007;27:1859–67.PubMedCrossRefGoogle Scholar
  101. Langer C, Radmacher MD, Ruppert AS, et al. High baalc expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a cancer and leukemia group B (CALGB) study. Blood. 2008;111:5371–9.PubMedCrossRefGoogle Scholar
  102. 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.PubMedCrossRefGoogle Scholar
  103. Leaman D, Chen PY, Fak J, et al. Sense-mediated depletion reveals essential and specific functions of microRNAs in drosophila development. Cell. 2005;121:1097–108.PubMedCrossRefGoogle Scholar
  104. Lebanony D, Benjamin H, Gilad S, et al. Diagnostic assay based on hsa-miR-205 expression distinguishes squamous from nonsquamous non-small-cell lung carcinoma. J Clin Oncol. 2009;27:2030–7.PubMedCrossRefGoogle Scholar
  105. Lee YB, Bantounas I, Lee DY, et al. Twist-1 regulates the miR-199a/214 cluster during development. Nucleic Acids Res. 2009b;37:123–8.PubMedCrossRefGoogle Scholar
  106. Lee KH, Chen YL, Yeh SD, et al. MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer cells through E2F1-mediated suppression of AKT phosphorylation. Oncogene. 2009a;28:3360–70.PubMedCrossRefGoogle Scholar
  107. Lei Z, Li B, Yang Z, et al. Regulation of HIF-1alpha and VEGF by miR-20b tunes tumor cells to adapt to the alteration of oxygen concentration. PLoS One. 2009;4:e7629.PubMedCrossRefGoogle Scholar
  108. Li N, Fu H, Tie Y, et al. MiR-34a inhibits migration and invasion by down-regulation of c-MET expression in human hepatocellular carcinoma cells. Cancer Lett. 2009b;275:44–53.PubMedCrossRefGoogle Scholar
  109. Li C, Jackson RM. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol. 2002;282:C227–C41.PubMedGoogle Scholar
  110. Li C, Kim SW, Rai D, et al. Copy number abnormalities, myc activity, and the genetic fingerprint of normal B cells mechanistically define the microRNA profile of diffuse large B-cell lymphoma. Blood. 2009a;113:6681–90.PubMedCrossRefGoogle Scholar
  111. Li Y, Li W, Yang Y, Lu Y, et al. MicroRNA-21 targets LRRFIP1 and contributes to VM-26 resistance in glioblastoma multiforme. Brain Res. 2009c;1286:13–8.PubMedCrossRefGoogle Scholar
  112. Li Y, VandenBoom TG 2nd, Kong D, et al. Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells. Cancer Res. 2009d;69:6704–12.PubMedCrossRefGoogle Scholar
  113. Li Y, Zhu X, Gu J, et al. Anti-miR-21 oligonucleotide sensitizes leukemic K562 cells to arsenic trioxide by inducing apoptosis. Cancer Sci. 2010;101:948–54.PubMedCrossRefGoogle Scholar
  114. Liang K, Lu Y, Jin W, et al. Sensitization of breast cancer cells to radiation by trastuzumab. Mol Cancer Ther. 2003;2:1113–20.PubMedGoogle Scholar
  115. 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;79:817–24.PubMedCrossRefGoogle Scholar
  116. Liu Q, Gazitt Y. Potentiation of dexamethasone-, paclitaxel-, and Ad-p53-induced apoptosis by Bcl-2 sense oligodeoxynucleotides in drug-resistant multiple myeloma cells. Blood. 2003;101:4105–14.PubMedCrossRefGoogle Scholar
  117. Liu CJ, Kao SY, Tu HF, et al. Increase of microRNA miR-31 level in plasma could be a potential marker of oral cancer. Oral Dis. 2010;16:360–4.PubMedCrossRefGoogle Scholar
  118. Lodes MJ, Caraballo M, Suciu D, et al. Detection of cancer with serum miRNAs on an oligonucleotide microarray. PLoS One. 2009;4:e6229.PubMedCrossRefGoogle Scholar
  119. Lowery AJ, Miller N, Devaney A, et al. MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/NEU receptor status in breast cancer. Breast Cancer Res. 2009;11:R27.PubMedCrossRefGoogle Scholar
  120. Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.PubMedCrossRefGoogle Scholar
  121. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449:682–8.PubMedCrossRefGoogle Scholar
  122. Ma L, Young J, Prabhala H, et al. MiR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010;12:247–56.PubMedGoogle Scholar
  123. Manni I, Artuso S, Careccia S, et al. The microRNA miR-92 increases proliferation of myeloid cells and by targeting p63 modulates the abundance of its isoforms. FASEB J. 2009;23:3957–66.PubMedCrossRefGoogle Scholar
  124. Mauceri HJ, Hanna NN, Beckett MA, et al. Combined effects of angiostatin and ionizing radiation in tumour therapy. Nature. 1998;394:287–91.PubMedCrossRefGoogle Scholar
  125. Mei M, Ren Y, Zhou X, et al. Down-regulation of miR-21 enhances chemotherapeutic effect of taxol in breast carcinoma cells. Technol Cancer Res Treat. 2010;9:77–86.PubMedGoogle Scholar
  126. Meiri E, Levy A, Benjamin H, et al. Discovery of microRNAs and other small RNAs in solid tumors. Nucleic Acids Res. 2010;38:6234–46.PubMedGoogle Scholar
  127. Melkonyan HS, Feaver WJ, Meyer E, et al. Transrenal nucleic acids: from proof of principle to clinical tests. Ann NY Acad Sci. 2008;1137:73–81.PubMedCrossRefGoogle Scholar
  128. Meng F, Henson R, Lang M, et al. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology. 2006;130:2113–29.PubMedCrossRefGoogle Scholar
  129. Meng F, Henson R, Wehbe-Janek H, et al. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133:647–58.PubMedCrossRefGoogle Scholar
  130. Mercatelli N, Coppola V, Bonci D, et al. The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice. PLoS One. 2008;3:e4029.PubMedCrossRefGoogle Scholar
  131. Michael A, Bajracharya SD, Yuen PS, et al. Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis. 2010;16:34–8.PubMedCrossRefGoogle Scholar
  132. Migliore C, Petrelli A, Ghiso E, et al. MicroRNAs impair MET-mediated invasive growth. Cancer Res. 2008;68:10128–36.PubMedCrossRefGoogle Scholar
  133. Milas L, Fan Z, Andratschke NH, et al. Epidermal growth factor receptor and tumor response to radiation: in vivo preclinical studies. Int J Radiat Oncol Biol Phys. 2004;58:966–71.PubMedCrossRefGoogle Scholar
  134. Milas L, Mason KA, Ang KK. Epidermal growth factor receptor and its inhibition in radiotherapy: in vivo findings. Int J Radiat Biol. 2003;79:539–45.PubMedCrossRefGoogle Scholar
  135. Miller TE, Ghoshal K, Ramaswamy B, et al. MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem. 2008;283:29897–903.PubMedCrossRefGoogle Scholar
  136. Mishra PJ, Humeniuk R, Longo-Sorbello GS, et al. A miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance. Proc Natl Acad Sci USA. 2007;104:13513–8.PubMedCrossRefGoogle Scholar
  137. 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.CrossRefGoogle Scholar
  138. Mott JL, Kobayashi S, Bronk SF, et al. MiR-29 regulates MCL-1 protein expression and apoptosis. Oncogene. 2007;26:6133–40.PubMedCrossRefGoogle Scholar
  139. Muth M, Theophile K, Hussein K, et al. Hypoxia-induced down-regulation of microRNA-449a/b impairs control over targeted serpine1 (PAI-1) mRNA – a mechanism involved in serpine1 (PAI-1) over-expression. J Transl Med. 2010;8:33.PubMedCrossRefGoogle Scholar
  140. Nakajima G, Hayashi K, Xi Y, et al. Non-coding microRNAs hsa-let-7 g and hsa-miR-181b are associated with chemoresponse to S-1 in colon cancer. Cancer Genomics Proteomics. 2006;3:317–24.PubMedGoogle Scholar
  141. Nakanishi T, Chumsri S, Khakpour N, et al. Side-population cells in luminal-type breast cancer have tumour-initiating cell properties, and are regulated by HER2 expression and signalling. Br J Cancer. 2010;102:815–26.PubMedCrossRefGoogle Scholar
  142. Nana-Sinkam P, Croce CM. MicroRNAs in diagnosis and prognosis in cancer: what does the future hold? Pharmacogenomics. 2010;11:667–9.PubMedCrossRefGoogle Scholar
  143. Nasser MW, Datta J, Nuovo G, et al. Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1. J Biol Chem. 2008;283:33394–405.PubMedCrossRefGoogle Scholar
  144. Noguchi K, Katayama K, Mitsuhashi J, et al. Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. Adv Drug Deliv Rev. 2009;61:26–33.PubMedCrossRefGoogle Scholar
  145. Noonan EJ, Place RF, Pookot D, et al. MiR-449a targets HDAC-1 and induces growth arrest in prostate cancer. Oncogene. 2009;28:1714–24.PubMedCrossRefGoogle Scholar
  146. Oh JS, Kim JJ, Byun JY, et al. Lin28-let7 modulates radiosensitivity of human cancer cells with activation of k-Ras. Int J Radiat Oncol Biol Phys. 2010;76:5–8.PubMedCrossRefGoogle Scholar
  147. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26.PubMedCrossRefGoogle Scholar
  148. 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. 2009;75:1374–9.PubMedCrossRefGoogle Scholar
  149. Pang RT, Leung CO, Ye TM, et al. MicroRNA-34a suppresses invasion through down-regulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. Carcinogenesis. 2010;31:1037–44.PubMedCrossRefGoogle Scholar
  150. Paoluzzi L, Gonen M, Bhagat G, et al. The BH3-only mimetic ABT-737 synergizes the neoplastic activity of proteasome inhibitors in lymphoid malignancies. Blood. 2008a;112:2906–16.PubMedCrossRefGoogle Scholar
  151. Paoluzzi L, Gonen M, Gardner JR, et al. Targeting bcl-2 family members with the BH3 mimetic at-101 markedly enhances the therapeutic effects of chemotherapeutic agents in in vitro and in vivo models of B-cell lymphoma. Blood. 2008b;111:5350–8.PubMedCrossRefGoogle Scholar
  152. Pardo OE, Latigo J, Jeffery RE, et al. The fibroblast growth factor receptor inhibitor PD173074 blocks small cell lung cancer growth in vitro and in vivo. Cancer Res. 2009;69:8645–51.PubMedCrossRefGoogle Scholar
  153. Park JK, Lee EJ, Esau C, et al. sense inhibition of microRNA-21 or -221 arrests cell cycle, induces apoptosis, and sensitizes the effects of gemcitabine in pancreatic adenocarcinoma. Pancreas. 2009a;38:e190–9.PubMedCrossRefGoogle Scholar
  154. Park SM, Shell S, Radjabi AR, et al. Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2. Cell Cycle. 2007;6:2585–90.PubMedCrossRefGoogle Scholar
  155. Park NJ, Zhou H, Elashoff D, et al. Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res. 2009b;15:5473–7.PubMedCrossRefGoogle Scholar
  156. Patnaik SK, Kannisto E, Knudsen S, et al. Evaluation of microRNA expression profiles that may predict recurrence of localized stage I non-small cell lung cancer after surgical resection. Cancer Res. 2010;70:36–45.PubMedCrossRefGoogle Scholar
  157. Pawlik TM, Keyomarsi K. Role of cell cycle in mediating sensitivity to radiotherapy. Int J Radiat Oncol Biol Phys. 2004;59:928–42.PubMedCrossRefGoogle Scholar
  158. Pekarsky Y, Santanam U, Cimmino A, et al. TCL1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res. 2006;66(24):11590–3.PubMedCrossRefGoogle Scholar
  159. Peter ME. Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle. 2009;8:843–52.PubMedCrossRefGoogle Scholar
  160. Petillo D, Kort EJ, Anema J, et al. MicroRNA profiling of human kidney cancer subtypes. Int J Oncol. 2009;35:109–14.PubMedCrossRefGoogle Scholar
  161. Petrocca F, Visone R, Onelli MR, et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008;13:272–86.PubMedCrossRefGoogle Scholar
  162. Pietras RJ, Poen JC, Gallardo D, et al. Monoclonal antibody to HER-2/NEU receptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells over-expressing this oncogene. Cancer Res. 1999;59:1347–55.PubMedGoogle Scholar
  163. Pigazzi M, Manara E, Baron E, et al. MiR-34b targets cyclic AMP-responsive element binding protein in acute myeloid leukemia. Cancer Res. 2009;69:2471–8.PubMedCrossRefGoogle Scholar
  164. Pineau P, Volinia S, McJunkin K, et al. MiR-221 over-expression contributes to liver tumorigenesis. Proc Natl Acad Sci USA. 2010;107:264–9.PubMedCrossRefGoogle Scholar
  165. Porkka KP, Pfeiffer MJ, Waltering KK, et al. MicroRNA expression profiling in prostate cancer. Cancer Res. 2007;67:6130–5.PubMedCrossRefGoogle Scholar
  166. Rainer J, Ploner C, Jesacher S, et al. Glucocorticoid-regulated microRNAs and mirtrons in acute lymphoblastic leukemia. Leukemia. 2009;23:746–52.PubMedCrossRefGoogle Scholar
  167. Ren Y, Kang CS, Yuan XB, et al. Co-delivery of as-miR-21 and 5-FU by poly(amidoamine) dendrimer attenuates human glioma cell growth in vitro. J Biomater Sci Polym Ed. 2010;21:303–14.PubMedCrossRefGoogle Scholar
  168. Resnick KE, Alder H, Hagan JP, et al. The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time pcr platform. Gynecol Oncol. 2009;112:55–9.PubMedCrossRefGoogle Scholar
  169. Rodriguez-Gonzalez FG, Sieuwerts AM, Smid M, et al. MicroRNA-34a suppresses invasion through down-regulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. Breast Cancer Res Treat. 2010;31:1037–44.Google Scholar
  170. Rosenwald S, Gilad S, Benjamin S, et al. Validation of a microRNA-based qRT-PCR test for accurate identification of tumor tissue origin. Mod Pathol. 2010;23:814–23.PubMedCrossRefGoogle Scholar
  171. Rossi G, Papotti M, Barbareschi M, et al. Morphology and a limited number of immunohistochemical markers may efficiently subtype non-small-cell lung cancer. J Clin Oncol. 2009;27:e.CrossRefGoogle Scholar
  172. Royds JA, Dower SK, Qwarnstrom EE, et al. Response of tumour cells to hypoxia: role of p53 and NFKB. Mol Pathol. 1998;51:55–61.PubMedCrossRefGoogle Scholar
  173. Rui W, Bing F, Hai-Zhu S, et al. Identification of microRNA profiles in docetaxel-resistant human non-small cell lung carcinoma cells (SPC-A1). J Cell Mol Med. 2010;14:206–14.PubMedCrossRefGoogle Scholar
  174. Salerno E, Scaglione BJ, Coffman FD, et al. Correcting miR-15a/16 genetic defect in new zealand black mouse model of CLL enhances drug sensitivity. Mol Cancer Ther. 2009;8:2684–92.PubMedCrossRefGoogle Scholar
  175. San Jose-Eneriz E, Roman-Gomez J, Jimenez-Velasco A, et al. MicroRNA expression profiling in imatinib-resistant chronic myeloid leukemia patients without clinically significant ABL1-mutations. Mol Cancer. 2009;8:69.PubMedCrossRefGoogle Scholar
  176. Sarkar FH, Li Y, Wang Z, et al. Pancreatic cancer stem cells and EMT in drug resistance and metastasis. Minerva Chir. 2009;64:489–500.PubMedGoogle Scholar
  177. Sayed D, He M, Hong C, et al. MicroRNA-21 is a downstream effector of AKT that mediates its apoptotic effects via suppression of Fas ligand. J Biol Chem. 2010;285:20281–90.PubMedCrossRefGoogle Scholar
  178. Schepeler T, Reinert JT, Ostenfeld MS, et al. Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res. 2008;68:6416–24.PubMedCrossRefGoogle Scholar
  179. Seike M, Goto A, Okano T, et al. MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers. Proc Natl Acad Sci USA. 2009;106:12085–90.PubMedCrossRefGoogle Scholar
  180. Semenza GL. Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit Rev Biochem Mol Biol. 2000;35:71–103.PubMedCrossRefGoogle Scholar
  181. Shah MA, Schwartz GK. Cyclin-dependent kinases as targets for cancer therapy. Cancer Chemother Biol Response Modif. 2003;21:145–70.PubMedGoogle Scholar
  182. Sharma SV, Lee DY, Li B, et al. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell. 2010;141:69–80.PubMedCrossRefGoogle Scholar
  183. Shell S, Park SM, Radjabi AR, et al. Let-7 expression defines two differentiation stages of cancer. Proc Natl Acad Sci USA. 2007;104:11400–5.PubMedCrossRefGoogle Scholar
  184. Shimizu S, Takehara T, Hikita H, et al. The let-7 family of microRNAs inhibits bcl-xl expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma. J Hepatol. 2010;52:698–704.PubMedCrossRefGoogle Scholar
  185. Siemann DW, Rojiani AM. Enhancement of radiation therapy by the novel vascular targeting agent ZD6126. Int J Radiat Oncol Biol Phys. 2002;53:164–71.PubMedCrossRefGoogle Scholar
  186. Song S, Wientjes MG, Gan Y, et al. Fibroblast growth factors: an epigenetic mechanism of broad spectrum resistance to cancer drugs. Proc Natl Acad Sci USA. 2000;2000(97):8658–63.CrossRefGoogle Scholar
  187. Sorrentino A, Liu CG, Addario A, et al. Role of microRNAs in drug-resistant ovarian cancer cells. Gynecol Oncol. 2008;111:478–86.PubMedCrossRefGoogle Scholar
  188. Stolz C, Hess G, Hahnel PS, et al. Targeting bcl-2 family proteins modulates the sensitivity of B-cell lymphoma to rituximab-induced apoptosis. Blood. 2008;112:3312–21.PubMedCrossRefGoogle Scholar
  189. Sun F, Fu H, Liu Q, et al. Down-regulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest. FEBS Lett. 2008;582:1564–8.PubMedCrossRefGoogle Scholar
  190. Sun T, Wang Q, Balk S, et al. The role of microRNA-221 and microRNA-222 in androgen-independent prostate cancer cell lines. Cancer Res. 2009;69:3356–63.PubMedCrossRefGoogle Scholar
  191. Sun Z, Zhao Z, Li G, et al. Relevance of two genes in the multidrug resistance of hepatocellular carcinoma: in vivo and clinical studies. Tumori. 2010;96:90–6.PubMedGoogle Scholar
  192. Svoboda M, Izakovicova Holla L, Sefr R, et al. Micro-RNAs miR125b and miR137 are frequently up-regulated in response to capecitabine chemoradiotherapy of rectal cancer. Int J Oncol. 2008;33:541–7.PubMedGoogle Scholar
  193. Sylvestre Y, De Guire V, Querido E, et al. An E2F/miR-20a autoregulatory feedback loop. J Biol Chem. 2007;282:2135–43.PubMedCrossRefGoogle Scholar
  194. Taguchi A, Yanagisawa K, Tanaka M, et al. Identification of hypoxia-inducible factor-1 alpha as a novel target for miR-17-92 microRNA cluster. Cancer Res. 2008;68:5540–5.PubMedCrossRefGoogle Scholar
  195. Takeshita F, Patrawala L, Osaki M, et al. Systemic delivery of synthetic microRNA-16 inhibits the growth of metastatic prostate tumors via down-regulation of multiple cell-cycle genes. Mol Ther. 2010;18:181–7.PubMedCrossRefGoogle Scholar
  196. Tarasov V, Jung P, Verdoodt B, et al. Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle. 2007;6:1586–93.PubMedCrossRefGoogle Scholar
  197. Tavazoie SF, Alarcon C, Oskarsson T, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451:147–52.PubMedCrossRefGoogle Scholar
  198. Tazawa H, Tsuchiya N, Izumiya M, et al. Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci USA. 2007;104:15472–7.PubMedCrossRefGoogle Scholar
  199. Thariat J, Yildirim G, Mason KA, et al. Combination of radiotherapy with EGFR antagonists for head and neck carcinoma. Int J Clin Oncol. 2007;12:99–110.PubMedCrossRefGoogle Scholar
  200. Tian Y, Luo A, Cai Y, et al. MicroRNA-10b promotes migration and invasion through KLF4 in human esophageal cancer cell lines. J Biol Chem. 2010;285:7986–94.PubMedCrossRefGoogle Scholar
  201. To K, Fotovati A, Reipas KM, et al. Y-box binding protein-1 induces the expression of CD44 and CD49f leading to enhanced self-renewal, mammosphere growth, and drug resistance. Cancer Res. 2010;70:2840–51.PubMedCrossRefGoogle Scholar
  202. To KK, Robey RW, Knutsen T, et al. Escape from hsa-miR-519c enables drug-resistant cells to maintain high expression of ABCG2. Mol Cancer Ther. 2009;8:2959–68.PubMedCrossRefGoogle Scholar
  203. Todaro M, Francipane MG, Medema JP, et al. Colon cancer stem cells: promise of targeted therapy. Gastroenterology. 2010;138:2151–62.PubMedCrossRefGoogle Scholar
  204. Trang P, Medina PP, Wiggins JF, et al. Regression of murine lung tumors by the let-7 microRNA. Oncogene. 2010;29:1580–7.PubMedCrossRefGoogle Scholar
  205. Tryndyak VP, Beland FA, Pogribny IP. E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells. Int J Cancer. 2010;126:2575–83.PubMedGoogle Scholar
  206. Tsang WP, Kwok TT. Let-7a microRNA suppresses therapeutics-induced cancer cell death by targeting caspase-3. Apoptosis. 2008;13:1215–22.PubMedCrossRefGoogle Scholar
  207. Varnholt H, Drebber U, Schulze F, et al. MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma. Hepatology. 2008;47:1223–32.PubMedCrossRefGoogle Scholar
  208. Viktorsson K, De Petris L, Lewensohn R. The role of p53 in treatment responses of lung cancer. Biochem Biophys Res Commun. 2005;331:868–80.PubMedCrossRefGoogle Scholar
  209. Visone R, Pallante P, Vecchione A, et al. Specific microRNAs are down-regulated in human thyroid anaplastic carcinomas. Oncogene. 2007a;26:7590–5.PubMedCrossRefGoogle Scholar
  210. Visone R, Russo L, Pallante P, et al. MicroRNAs (miR)-221 and miR-222, both over-expressed in human thyroid papillary carcinomas, regulate p27/Kip1 protein levels and cell cycle. Endocr Relat Cancer. 2007b;14:791–8.PubMedCrossRefGoogle Scholar
  211. Vokes EE, Chu E. Anti-EGFR therapies: clinical experience in colorectal, lung, and head and neck cancers. Oncology (Williston Park). 2006;20(5 Suppl 2):15–25.Google Scholar
  212. Wagner-Ecker M, Schwager C, Wirkner U, et al. MicroRNA expression after ionizing radiation in human endothelial cells. Radiat Oncol. 2010;5:25.PubMedCrossRefGoogle Scholar
  213. Wang GL, Jiang BH, Rue EA, et al. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-pas heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA. 1995;92:5510–4.PubMedCrossRefGoogle Scholar
  214. Weidhaas JB, Babar I, Nallur SM, et al. MicroRNAs as potential agents to alter resistance to cytotoxic cancer therapy. Cancer Res. 2007;67:11111–6.PubMedCrossRefGoogle Scholar
  215. Weiss GJ, Bemis LT, Nakajima E, et al. EGFR regulation by microRNA in lung cancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines. Ann Oncol. 2008;19:1053–9.PubMedCrossRefGoogle Scholar
  216. Wiklund ED, Bramsen JB, Hulf T, et al. Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer. Int J Cancer. 2010. doi:10.1002/ijc.25461.Google Scholar
  217. 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. 2008;123:372–9.PubMedCrossRefGoogle Scholar
  218. Xie Y, Todd NW, Liu Z, et al. Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer. Lung Cancer. 2010;67:170–6.PubMedCrossRefGoogle Scholar
  219. Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene. 2007;26:5541–52.PubMedCrossRefGoogle Scholar
  220. Yamakuchi M, Ferlito M, Lowenstein CJ. MiR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci USA. 2008;105:13421–6.PubMedCrossRefGoogle Scholar
  221. Yan LX, Huang XF, Shao Q, et al. MicroRNA miR-21 over-expression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA. 2008;14:2348–60.PubMedCrossRefGoogle Scholar
  222. Yang Z, Chen S, Luan X, et al. MicroRNA-214 is aberrantly expressed in cervical cancers and inhibits the growth of HeLa cells. IUBMB Life. 2009c;61:1075–82.PubMedCrossRefGoogle Scholar
  223. Yang X, Feng M, Jiang X, et al. MiR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate PRB-E2F1 activity through a feedback loop by targeting CDK6 and CDC25A. Genes Dev. 2009b;23:2388–93.PubMedCrossRefGoogle Scholar
  224. Yang K, Handorean AM, Iczkowski KA. MicroRNAs 373 and 520c are down-regulated in prostate cancer, suppress CD44 translation and enhance invasion of prostate cancer cells in vitro. Int J Clin Exp Pathol. 2009a;2:361–9.PubMedGoogle Scholar
  225. Yang N, Kaur S, Volinia S, et al. MicroRNA microarray identifies let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Res. 2008b;68:10307–14.PubMedCrossRefGoogle Scholar
  226. 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. 2008a;68:425–33.PubMedCrossRefGoogle Scholar
  227. Yu SL, Chen HY, Chang GC, et al. MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell. 2008;13:48–57.PubMedCrossRefGoogle Scholar
  228. Yu SL, Chen HY, Yang PC, et al. Unique microRNA signature and clinical outcome of cancers. DNA Cell Biol. 2007;26:283–92.PubMedCrossRefGoogle Scholar
  229. Yu L, Todd NW, Xing L, et al. Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int J Cancer. 2010;127:2870–8.Google Scholar
  230. Zenz T, Mohr J, Eldering E, et al. MiR-34a as part of the resistance network in chronic lymphocytic leukemia. Blood. 2009;113:3801–8.PubMedCrossRefGoogle Scholar
  231. Zhang HT, Craft P, Scott PA, et al. Enhancement of tumor growth and vascular density by transfection of vascular endothelial cell growth factor into MCF-7 human breast carcinoma cells. J Natl Cancer Inst. 1995;87:213–9.PubMedCrossRefGoogle Scholar
  232. Zhang C, Kang C, You Y, et al. Co-suppression of miR-221/222 cluster suppresses human glioma cell growth by targeting p27Kip1 in vitro and in vivo. Int J Oncol. 2009;34:1653–60.PubMedCrossRefGoogle Scholar
  233. Zhao JJ, Lin J, Yang H, et al. MicroRNA-221/222 negatively regulates estrogen receptor alpha and is associated with tamoxifen resistance in breast cancer. J Biol Chem. 2008;283:31079–86.PubMedCrossRefGoogle Scholar
  234. Zhong M, Ma X, Sun C, et al. MicroRNAs reduce tumor growth and contribute to enhance cytotoxicity induced by gefitinib in non-small cell lung cancer. Chem Biol Interact. 2010;184:431–8.PubMedCrossRefGoogle Scholar
  235. Zhou M, Liu Z, Zhao Y, et al. MicroRNA-125b confers the resistance of breast cancer cells to paclitaxel through suppression of pro-apoptotic bcl-2 antagonist killer 1 (BAK1). J Biol Chem. 2010;285:21496–507.PubMedCrossRefGoogle Scholar
  236. Zhu W, Qin W, Atasoy U, et al. Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes. 2009;2:89.PubMedCrossRefGoogle Scholar
  237. Zhu S, Si ML, Wu H, et al. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem. 2007;282:14328–36.PubMedCrossRefGoogle Scholar
  238. Zubakov D, Boersma AW, Choi Y, et al. MicroRNA markers for forensic body fluid identification obtained from microarray screening and quantitative RT-PCR confirmation. Int J Legal Med. 2010;124:217–26.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Netherlands 2011

Authors and Affiliations

  • Emily J. Noonan
    • 1
  • Robert F. Place
    • 2
  • Long-Cheng Li
    • 2
  1. 1.Department of Medicine and Department of Hematology, Center for Molecular Biology in MedicineStanford University School of Medicine, Veterans Affairs Palo Alto Health Care SystemPalo AltoUSA
  2. 2.Department of UrologyHelen Diller Comprehensive Cancer Center, University of CaliforniaSan FranciscoUSA

Personalised recommendations