MicroRNAs: Master regulators of drug resistance, stemness, and metastasis

Journal of Molecular Medicine

Volumn 92, Issue 4, 2014, Pages 321-336

  Raza, Umar ^a   Zhang, Jitao David ^b   Şahin, Özgür ^a  

^a BILKENT UNIVERSITY   (Turkey)

^b F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Drug resistance; Epithelial mesenchymal transition; Metastasis; MicroRNAs; miRNA protein interaction networks; Stemness; Systems biomedicine

Indexed keywords

ALKALOID; ANTHRACYCLINE; ANTINEOPLASTIC ANTIMETABOLITE; CAMPTOTHECIN; CETUXIMAB; CHLORMETHINE; CISPLATIN; DOXORUBICIN; ERLOTINIB; FLUOROURACIL; FULVESTRANT; GEFITINIB; GEMCITABINE; IRINOTECAN; LETROZOLE; MICRORNA; MITOMYCIN; MITOXANTRONE; PACLITAXEL; PLATINUM COMPLEX; SUNITINIB; TAMOXIFEN; TAXANE DERIVATIVE; TEMOZOLOMIDE; TOPOTECAN; TRASTUZUMAB; VINBLASTINE;

BIOGENESIS; CANCER THERAPY; DRUG RESISTANCE; GENE EXPRESSION; HUMAN; METASTASIS; NONHUMAN; PROTEIN RNA BINDING; REVIEW; ANIMAL; CANCER STEM CELL; EPITHELIAL MESENCHYMAL TRANSITION; GENE EXPRESSION REGULATION; GENETICS; NEOPLASMS; PATHOLOGY; PHYSIOLOGY; RNA INTERFERENCE; SYSTEMS BIOLOGY;

ANIMALS; DRUG RESISTANCE, NEOPLASM; EPITHELIAL-MESENCHYMAL TRANSITION; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MICRORNAS; NEOPLASM METASTASIS; NEOPLASMS; NEOPLASTIC STEM CELLS; RNA INTERFERENCE; SYSTEMS BIOLOGY;

EID: 84898465843     PISSN: 09462716     EISSN: 14321440     Source Type: Journal    
DOI: 10.1007/s00109-014-1129-2     Document Type: Review

References (180)

1. He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522-531
2. Singh SK, Pal Bhadra M, Girschick HJ, Bhadra U (2008) MicroRNAs-micro in size but macro in function. FEBS J 275:4929-4944
3. Inui M, Martello G, Piccolo S (2010) MicroRNA control of signal transduction. Nat Rev Mol Cell Biol 11:252-263
4. Kozomara A, Griffiths-Jones S (2011) miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 39:D152-D157
5. Borchert GM, Lanier W, Davidson BL (2006) RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol 13:1097-1101
6. Bohnsack MT, Czaplinski K, Gorlich D (2004) Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 10:185-191
7. Orom UA, Nielsen FC, Lund AH (2008) MicroRNA-10a binds the 5UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell 30:460-471
8. Forman JJ, Legesse-Miller A, Coller HA (2008) A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proc Natl Acad Sci U S A 105:14879-14884
9. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M et al (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 101:2999-3004
10. Ambros V (2001) microRNAs: tiny regulators with great potential. Cell 107:823-826
11. Friedman RC, Farh KK, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92-105
12. Zhang B, Pan X, Cobb GP, Anderson TA (2007) microRNAs as oncogenes and tumor suppressors. Dev Biol 302:1-12
13. Jin HY, Oda H, Lai M, Skalsky RL, Bethel K, Shepherd J, Kang SG, Liu WH, Sabouri-Ghomi M, Cullen BR et al (2013) MicroRNA-17 92 plays a causative role in lymphomagenesis by coordinating multiple oncogenic pathways. EMBO J 32:2377-2391
14. D'Amato NC, Howe EN, Richer JK (2013) MicroRNA regulation of epithelial plasticity in cancer. Cancer Lett 341:46-55
15. Ludwig K, Fassan M, Mescoli C, Pizzi M, Balistreri M, Albertoni L, Pucciarelli S, Scarpa M, Sturniolo GC, Angriman I et al (2013) PDCD4/miR-21 dysregulation in inflammatory bowel disease-associated carcinogenesis. Virchows Arch 462:57-63
16. Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY (2007) miR-21-mediated tumor growth. Oncogene 26:2799-2803
17. Medina PP, Nolde M, Slack FJ (2010) OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature 467:86-90
18. Gironella M, Seux M, Xie MJ, Cano C, Tomasini R, Gommeaux J, Garcia S, Nowak J, Yeung ML, Jeang KT et al (2007) Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci U S A 104:16170-16175
19. Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ (2005) RAS is regulated by the let-7 microRNA family. Cell 120:635-647
20. Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, Wilson M, Wang X, Shelton J, Shingara J et al (2007) The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res 67:7713-7722
21. Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N, Bentwich Z, Oren M (2007) Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell 26:731-743
22. Kasinski AL, Slack FJ (2011) Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer 11:849-864
23. Malhotra V, Perry MC (2003) Classical chemotherapy: mechanisms, toxicities and the therapeutic window. Cancer Biol Ther 2:S2-S4
24. Gerber DE (2008) Targeted therapies: a new generation of cancer treatments. Am Fam Physician 77:311-319
25. Burris HA 3rd, Rugo HS, Vukelja SJ, Vogel CL, Borson RA, Limentani S, Tan-Chiu E, Krop IE, Michaelson RA, Girish S et al (2011) Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol 29:398-405
26. Lippert TH, Ruoff HJ, Volm M (2008) Intrinsic and acquired drug resistance in malignant tumors. The main reason for therapeutic failure. Arzneim Forsch 58:261-264
27. Gottesman MM (2002) Mechanisms of cancer drug resistance. Annu Rev Med 53:615-627
28. Dhillon KK, Swisher EM, Taniguchi T (2011) Secondary mutations of BRCA1/2 and drug resistance. Cancer Sci 102:663-669
29. Zhou Q, Lv H, Mazloom AR, Xu H, Ma'ayan A, Gallo JM (2012) Activation of alternate prosurvival pathways accounts for acquired sunitinib resistance in U87MG glioma xenografts. J Pharm Exp Ther 343:509-519
30. Blower PE, Chung JH, Verducci JS, Lin S, Park JK, Dai Z, Liu CG, Schmittgen TD, Reinhold WC, Croce CM et al (2008) MicroRNAs modulate the chemosensitivity of tumor cells. Mol Cancer Ther 7:1-9
31. Cai J, Yang C, Yang Q, Ding H, Jia J, Guo J, Wang J, Wang Z (2013) Deregulation of let-7e in epithelial ovarian cancer promotes the development of resistance to cisplatin. Oncogenesis 2:e75
32. Weeraratne SD, Amani V, Neiss A, Teider N, Scott DK, Pomeroy SL, Cho YJ (2011) miR-34a confers chemosensitivity through modulation of MAGE-A and p53 in medulloblastoma. Neuro Oncol 13:165-175
33. Takwi AA, Wang YM, Wu J, Michaelis M, Cinatl J, Chen T (2013) miR-137 regulates the constitutive androstane receptor and modulates doxorubicin sensitivity in parental and doxorubicin-resistant neuroblastoma cells. Oncogene. doi: 10.1038/onc.2013.330
34. Pouliot LM, Shen DW, Suzuki T, Hall MD, Gottesman MM (2013) Contributions of microRNA dysregulation to cisplatin resistance in adenocarcinoma cells. Exp Cell Res 319:566-574
35. Druker BJ (2003) Imatinib mesylate in the treatment of chronic myeloid leukaemia. Expert Opin Pharmacother 4:963-971
36. Xu C, Fu H, Gao L, Wang L, Wang W, Li J, Li Y, Dou L, Gao X, Luo X et al (2012) BCR-ABL/GATA1/miR-138 mini circuitry contributes to the leukemogenesis of chronic myeloid leukemia. Oncogene 33:44-54
37. Li Y, Yuan Y, Tao K, Wang X, Xiao Q, Huang Z, Zhong L, Cao W, Wen J, Feng W (2013) Inhibition of BCR/ABL protein expression by miR-203 sensitizes for imatinib mesylate. PLoS ONE 8:e61858
38. Gong C, Yao Y, Wang Y, Liu B, Wu W, Chen J, Su F, Yao H, Song E (2011) Up-regulation of miR-21 mediates resistance to trastuzumab therapy for breast cancer. J Biol Chem 286:19127-19137
39. Jung EJ, Santarpia L, Kim J, Esteva FJ, Moretti E, Buzdar AU, Di Leo A, Le XF, Bast RC Jr, Park ST et al (2012) Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. Cancer 118:2603-2614
40. Zhao JJ, Lin J, Yang H, Kong W, He L, Ma X, Coppola D, Cheng JQ (2008) MicroRNA-221/222 negatively regulates estrogen receptor alpha and is associated with tamoxifen resistance in breast cancer. J Biol Chem 283:31079-31086
41. Miller TE, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro CL, Jacob S, Majumder S (2008) MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem 283:29897-29903
42. Rao X, Di Leva G, Li M, Fang F, Devlin C, Hartman-Frey C, Burow ME, Ivan M, Croce CM, Nephew KP (2011) MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways. Oncogene 30:1082-1097
43. Ward A, Balwierz A, Zhang JD, Kublbeck M, Pawitan Y, Hielscher T, Wiemann S, Sahin O (2013) Re-expression of microRNA-375 reverses both tamoxifen resistance and accompanying EMT-like properties in breast cancer. Oncogene 32:1173-1182
44. Fidler IJ (2003) The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer 3:453-458
45. Dykxhoorn DM (2010) MicroRNAs and metastasis: little RNAs go a long way. Cancer Res 70:6401-6406
46. Tao ZH, Wan JL, Zeng LY, Xie L, Sun HC, Qin LX, Wang L, Zhou J, Ren ZG, Li YX et al (2013) miR-612 suppresses the invasive-metastatic cascade in hepatocellular carcinoma. J Exp Med 210:789-803
47. Polyak K, Weinberg RA (2009) Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 9:265-273
48. Gibbons DL, Lin W, Creighton CJ, Rizvi ZH, Gregory PA, Goodall GJ, Thilaganathan N, Du L, Zhang Y, Pertsemlidis A et al (2009) Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. Genes Dev 23:2140-2151
49. Olson P, Lu J, Zhang H, Shai A, Chun MG, Wang Y, Libutti SK, Nakakura EK, Golub TR, Hanahan D (2009) MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer. Genes Dev 23:2152-2165
50. Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon MF, Goodall GJ (2008) A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res 68:7846-7854
51. Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, Brabletz T (2008) A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep 9:582-589
52. Kim NH, Kim HS, Li XY, Lee I, Choi HS, Kang SE, Cha SY, Ryu JK, Yoon D, Fearon ER et al (2011) A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition. J Cell Biol 195:417-433
53. Siemens H, Jackstadt R, Hunten S, Kaller M, Menssen A, Gotz U, Hermeking H (2011) miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions. Cell Cycle 10:4256-4271
54. Jurmeister S, Baumann M, Balwierz A, Keklikoglou I, Ward A, Uhlmann S, Zhang JD, Wiemann S, Sahin O (2012) MicroRNA-200c represses migration and invasion of breast cancer cells by targeting actin-regulatory proteins FHOD1 and PPM1F. Mol Cell Biol 32:633-651
55. Li X, Roslan S, Johnstone CN, Wright JA, Bracken CP, Anderson M, Bert AG, Selth LA, Anderson RL, Goodall GJ et al (2013) MiR-200 can repress breast cancer metastasis through ZEB1-independent but moesin-dependent pathways. Oncogene. doi: 10.1038/onc.2013.370
56. Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, Allgayer H (2008) MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27:2128-2136
57. Valastyan S, Chang A, Benaich N, Reinhardt F, Weinberg RA (2010) Concurrent suppression of integrin alpha5, radixin, and RhoA phenocopies the effects of miR-31 on metastasis. Cancer Res 70:5147-5154
58. Okamoto K, Ishiguro T, Midorikawa Y, Ohata H, Izumiya M, Tsuchiya N, Sato A, Sakai H, Nakagama H (2012) miR-493 induction during carcinogenesis blocks metastatic settlement of colon cancer cells in liver. EMBO J 31:1752-1763
59. Cimino D, De Pitta C, Orso F, Zampini M, Casara S, Penna E, Quaglino E, Forni M, Damasco C, Pinatel E et al (2013) miR148b is a major coordinator of breast cancer progression in a relapse-associated microRNA signature by targeting ITGA5, ROCK1, PIK3CA, NRAS, and CSF1. FASEB J 27:1223-1235
60. Keklikoglou I, Koerner C, Schmidt C, Zhang JD, Heckmann D, Shavinskaya A, Allgayer H, Guckel B, Fehm T, Schneeweiss A et al (2012) MicroRNA-520/373 family functions as a tumor suppressor in estrogen receptor negative breast cancer by targeting NF-kappaB and TGF-beta signaling pathways. Oncogene 31:4150-4163
61. Nguyen DX, Bos PD, Massague J (2009) Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer 9:274-284
62. Korpal M, Ell BJ, Buffa FM, Ibrahim T, Blanco MA, Celia-Terrassa T, Mercatali L, Khan Z, Goodarzi H, Hua Y et al (2011) Direct targeting of Sec23a by miR-200 s influences cancer cell secretome and promotes metastatic colonization. Nat Med 17:1101-1108
63. Liu S, Tetzlaff MT, Cui R, Xu X (2012) miR-200c inhibits melanoma progression and drug resistance through down-regulation of BMI-1. Am J Pathol 181:1823-1835
64. Ceppi P, Mudduluru G, Kumarswamy R, Rapa I, Scagliotti GV, Papotti M, Allgayer H (2010) Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer. Mol Cancer Res 8:1207-1216
65. Li Y, VandenBoom TG 2nd, Kong D, Wang Z, Ali S, Philip PA, Sarkar FH (2009) 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 69:6704-6712
66. Cao M, Seike M, Soeno C, Mizutani H, Kitamura K, Minegishi Y, Noro R, Yoshimura A, Cai L, Gemma A (2012) MiR-23a regulates TGF-beta-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells. Int J Oncol 41:869-875
67. Xia H, Ooi LL, Hui KM (2013) MicroRNA-216a/217-induced epithelial-mesenchymal transition targets PTEN and SMAD7 to promote drug resistance and recurrence of liver cancer. Hepatology 58:629-641
68. Weissman IL (2000) Stem cells: units of development, units of regeneration, and units in evolution. Cell 100:157-168
69. Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ (2006) Purification and unique properties of mammary epithelial stem cells. Nature 439:993-997
70. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K et al (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114:763-776
71. Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730-737
72. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67:1030-1037
73. Maitland NJ, Collins AT (2008) Prostate cancer stem cells: a new target for therapy. J Clin Oncol Off J Am Soc Clin Oncol 26:2862-2870
74. O'Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106-110
75. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821-5828
76. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100:3983-3988
77. Yilmaz OH, Valdez R, Theisen BK, Guo W, Ferguson DO, Wu H, Morrison SJ (2006) Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 441:475-482
78. Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ (2008) Efficient tumour formation by single human melanoma cells. Nature 456:593-598
79. Xu XT, Xu Q, Tong JL, Zhu MM, Nie F, Chen X, Xiao SD, Ran ZH (2012) MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer. Br J Cancer 106:1320-1330
80. Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, Diehn M, Liu H, Panula SP, Chiao E et al (2009) Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138:592-603
81. Ju SY, Chiou SH, Su Y (2013) Maintenance of the stemness in CD44 HCT-15 and HCT-116 human colon cancer cells requires miR-203 suppression. Stem Cell Res 12:86-100
82. Golestaneh AF, Atashi A, Langroudi L, Shafiee A, Ghaemi N, Soleimani M (2012) miRNAs expressed differently in cancer stem cells and cancer cells of human gastric cancer cell line MKN-45. Cell Biochem Funct 30:411-418
83. Ji J, Yamashita T, Budhu A, Forgues M, Jia HL, Li C, Deng C, Wauthier E, Reid LM, Ye QH et al (2009) Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. Hepatology 50:472-480
84. Yu Y, Kanwar SS, Patel BB, Oh PS, Nautiyal J, Sarkar FH, Majumdar AP (2012) MicroRNA-21 induces stemness by downregulating transforming growth factor beta receptor 2 (TGFbetaR2) in colon cancer cells. Carcinogenesis 33:68-76
85. Li F, Tiede B, Massague J, Kang Y (2007) Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res 17:3-14
86. Xu CX, Xu M, Tan L, Yang H, Permuth-Wey J, Kruk PA, Wenham RM, Nicosia SV, Lancaster JM, Sellers TA et al (2012) MicroRNA miR-214 regulates ovarian cancer cell stemness by targeting p53/Nanog. J Biol Chem 287:34970-34978
87. Bourguignon LY, Wong G, Earle C, Chen L (2012) Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma. J Biol Chem 287:32800-32824
88. Bitarte N, Bandres E, Boni V, Zarate R, Rodriguez J, Gonzalez-Huarriz M, Lopez I, Javier Sola J, Alonso MM, Fortes P et al (2011) MicroRNA-451 is involved in the self-renewal, tumorigenicity, and chemoresistance of colorectal cancer stem cells. Stem Cells 29:1661-1671
89. Bao B, Ali S, Kong D, Sarkar SH, Wang Z, Banerjee S, Aboukameel A, Padhye S, Philip PA, Sarkar FH (2011) Anti-tumor activity of a novel compound-CDF is mediated by regulating miR-21, miR-200, and PTEN in pancreatic cancer. PLoS ONE 6:e17850
90. Bao B, Wang Z, Ali S, Ahmad A, Azmi AS, Sarkar SH, Banerjee S, Kong D, Li Y, Thakur S et al (2012) Metformin inhibits cell proliferation, migration and invasion by attenuating CSC function mediated by deregulating miRNAs in pancreatic cancer cells. Cancer Prev Res (Phila) 5:355-364
91. Lo WL, Yu CC, Chiou GY, Chen YW, Huang PI, Chien CS, Tseng LM, Chu PY, Lu KH, Chang KW et al (2011) MicroRNA-200c attenuates tumour growth and metastasis of presumptive head and neck squamous cell carcinoma stem cells. J Pathol 223:482-495
92. Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A, Waldvogel B, Vannier C, Darling D, zur Hausen A et al (2009) The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol 11:1487-1495
93. Okuda H, Xing F, Pandey PR, Sharma S, Watabe M, Pai SK, Mo YY, Iiizumi-Gairani M, Hirota S, Liu Y et al (2013) miR-7 suppresses brain metastasis of breast cancer stem-like cells by modulating KLF4. Cancer Res 73:1434-1444
94. Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S et al (2011) The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med 17:211-215
95. Song SJ, Poliseno L, Song MS, Ala U, Webster K, Ng C, Beringer G, Brikbak NJ, Yuan X, Cantley LC et al (2013) MicroRNA-antagonism regulates breast cancer stemness and metastasis via TET-family-dependent chromatin remodeling. Cell 154:311-324
96. Iliou MS, da Silva-Diz V, Carmona FJ, Ramalho-Carvalho J, Heyn H, Villanueva A, Munoz P, Esteller M (2013) Impaired DICER1 function promotes stemness and metastasis in colon cancer. Oncogene. doi: 10.1038/onc.2013.398
97. Pencheva N, Tavazoie SF (2013) Control of metastatic progression by microRNA regulatory networks. Nat Cell Biol 15:546-554
98. Vera J, Lai X, Schmitz U, Wolkenhauer O (2013) MicroRNA-regulated networks: the perfect storm for classical molecular biology, the ideal scenario for systems biology. Adv Exp Med Biol 774:55-76
99. Aguda BD, Kim Y, Piper-Hunter MG, Friedman A, Marsh CB (2008) MicroRNA regulation of a cancer network: consequences of the feedback loops involving miR-17-92, E2F, and Myc. Proc Natl Acad Sci U S A 105:19678-19683
100. Vera J, Schmitz U, Lai X, Engelmann D, Khan FM, Wolkenhauer O, Putzer BM (2013) Kinetic modeling-based detection of genetic signatures that provide chemoresistance via the E2F1-p73/DNp73-miR-205 network. Cancer Res 73:3511-3524
101. Prosser HM, Koike-Yusa H, Cooper JD, Law FC, Bradley A (2011) A resource of vectors and ES cells for targeted deletion of microRNAs in mice. Nature Biotechnol 29:840-845
102. Ye H, Liu X, Lv M, Wu Y, Kuang S, Gong J, Yuan P, Zhong Z, Li Q, Jia H et al (2012) MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia. Nucleic Acids Res 40:5201-5214
103. Ding X, Park SI, McCauley LK, Wang CY (2013) Signaling between transforming growth factor beta (TGF-beta) and transcription factor SNAI2 represses expression of microRNA miR-203 to promote epithelial-mesenchymal transition and tumor metastasis. J Biol Chem 288:10241-10253
104. Uhlmann S, Zhang JD, Schwager A, Mannsperger H, Riazalhosseini Y, Burmester S, Ward A, Korf U, Wiemann S, Sahin O (2010) miR-200bc/429 cluster targets PLCgamma1 and differentially regulates proliferation and EGF-driven invasion than miR-200a/141 in breast cancer. Oncogene 29:4297-4306
105. Tarasov V, Jung P, Verdoodt B, Lodygin D, Epanchintsev A, Menssen A, Meister G, Hermeking H (2007) 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 6:1586-1593
106. Leivonen SK, Rokka A, Ostling P, Kohonen P, Corthals GL, Kallioniemi O, Perala M (2011) Identification of miR-193b targets in breast cancer cells and systems biological analysis of their functional impact. Mol Cell Proteomics 10(M110):005322
107. Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP (2008) The impact of microRNAs on protein output. Nature 455:64-71
108. Li L, Xu J, Yang D, Tan X, Wang H (2010) Computational approaches for microRNA studies: a review. Mamm Genome 21:1-12
109. Min H, Yoon S (2010) Got target? Computational methods for microRNA target prediction and their extension. Exp Mol Med 42:233-244
110. Uhlmann S, Mannsperger H, Zhang JD, Horvat EA, Schmidt C, Kublbeck M, Henjes F, Ward A, Tschulena U, Zweig K et al (2012) Global microRNA level regulation of EGFR-driven cell-cycle protein network in breast cancer. Mol Syst Biol 8:570
111. Yu Z, Willmarth NE, Zhou J, Katiyar S, Wang M, Liu Y, McCue PA, Quong AA, Lisanti MP, Pestell RG (2010) microRNA 17/20 inhibits cellular invasion and tumor metastasis in breast cancer by heterotypic signaling. Proc Natl Acad Sci U S A 107:8231-8236
112. Volinia S, Galasso M, Costinean S, Tagliavini L, Gamberoni G, Drusco A, Marchesini J, Mascellani N, Sana ME, Abu Jarour R et al (2010) Reprogramming of miRNA networks in cancer and leukemia. Genome Res 20:589-599
113. Png KJ, Halberg N, Yoshida M, Tavazoie SF (2012) A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature 481:190-194
114. Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, Rothballer A, Ascano M Jr, Jungkamp AC, Munschauer M et al (2010) Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141:129-141
115. Nilsson T, Mann M, Aebersold R, Yates JR 3rd, Bairoch A, Bergeron JJ (2010) Mass spectrometry in high-throughput proteomics: ready for the big time. Nat methods 7:681-685
116. Sumazin P, Yang X, Chiu HS, Chung WJ, Iyer A, Llobet-Navas D, Rajbhandari P, Bansal M, Guarnieri P, Silva J et al (2011) An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Cell 147:370-381
117. Zacher B, Abnaof K, Gade S, Younesi E, Tresch A, Frohlich H (2012) Joint Bayesian inference of condition-specific miRNA and transcription factor activities from combined gene and microRNA expression data. Bioinformatics 28:1714-1720
118. Liu Y, Devescovi V, Chen S, Nardini C (2013) Multilevel omic data integration in cancer cell lines: advanced annotation and emergent properties. BMC Syst Biol 7:14
119. Rohr C, Kerick M, Fischer A, Kuhn A, Kashofer K, Timmermann B, Daskalaki A, Meinel T, Drichel D, Borno ST et al (2013) High-throughput miRNA and mRNA sequencing of paired colorectal normal, tumor and metastasis tissues and bioinformatic modeling of miRNA-1 therapeutic applications. PLoS ONE 8:e67461
120. Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell's functional organization. Nat Rev Genet 5:101-113
121. Barabasi AL, Gulbahce N, Loscalzo J (2011) Network medicine: a network-based approach to human disease. Nat Rev Genet 12:56-68
122. Alon U (2007) Network motifs: theory and experimental approaches. Nat Rev Genet 8:450-461
123. Zhang HM, Kuang S, Xiong X, Gao T, Liu C, Guo AY (2013) Transcription factor and microRNA co-regulatory loops: important regulatory motifs in biological processes and diseases. Brief Bioinform. doi: 10.1093/bib/bbt085
124. Zhang KL, Han L, Chen LY, Shi ZD, Yang M, Ren Y, Chen LC, Zhang JX, Pu PY, Kang CS (2014) Blockage of a miR-21/EGFR regulatory feedback loop augments anti-EGFR therapy in glioblastomas. Cancer Lett 342:139-149
125. Zhao X, Lwin T, Zhang X, Huang A, Wang J, Marquez VE, Chen-Kiang S, Dalton WS, Sotomayor E, Tao J (2013) Disruption of the MYC-miRNA-EZH2 loop to suppress aggressive B-cell lymphoma survival and clonogenicity. Leukemia. doi: 10.1038/leu.2013.94
126. Rukov JL, Wilentzik R, Jaffe I, Vinther J, Shomron N (2013) Pharmaco-miR: linking microRNAs and drug effects. Brief Bioinform. doi: 10.1093/bib/bbs082
127. Jiang Q, Wang Y, Hao Y, Juan L, Teng M, Zhang X, Li M, Wang G, Liu Y (2009) miR2Disease: a manually curated database for microRNA deregulation in human disease. Nucleic Acids Res 37:D98-D104
128. Pardo-Martin C, Chang TY, Koo BK, Gilleland CL, Wasserman SC, Yanik MF (2010) High-throughput in vivo vertebrate screening. Nat Methods 7:634-636
129. Garzon R, Marcucci G, Croce CM (2010) Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov 9:775-789
130. Hutvagner G, Simard MJ, Mello CC, Zamore PD (2004) Sequence-specific inhibition of small RNA function. PLoS Biol 2:E98
131. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M (2005) Silencing of microRNAs in vivo with 'antagomirs'. Nature 438:685-689
132. Zhang Y, Roccaro AM, Rombaoa C, Flores L, Obad S, Fernandes SM, Sacco A, Liu Y, Ngo H, Quang P et al (2012) LNA-mediated anti-miR-155 silencing in low-grade B-cell lymphomas. Blood 120:1678-1686
133. Esquela-Kerscher A, Trang P, Wiggins JF, Patrawala L, Cheng A, Ford L, Weidhaas JB, Brown D, Bader AG, Slack FJ (2008) The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle 7:759-764
134. Xiong Y, Fang JH, Yun JP, Yang J, Zhang Y, Jia WH, Zhuang SM (2010) Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology 51:836-845
135. Ell B, Mercatali L, Ibrahim T, Campbell N, Schwarzenbach H, Pantel K, Amadori D, Kang Y (2013) Tumor-Induced Osteoclast miRNA Changes as Regulators and Biomarkers of Osteolytic Bone Metastasis. Cancer Cell 24:542-556
136. Gumireddy K, Young DD, Xiong X, Hogenesch JB, Huang Q, Deiters A (2008) Small-molecule inhibitors of microrna miR-21 function. Angew Chem Int Ed Engl 47:7482-7484
137. Kota J, Chivukula RR, O'Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Vivekanandan P, Torbenson M, Clark KR et al (2009) Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137:1005-1017
138. Kumar MS, Erkeland SJ, Pester RE, Chen CY, Ebert MS, Sharp PA, Jacks T (2008) Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci U S A 105:3903-3908
139. Zhang Y, Wang Z, Gemeinhart RA (2013) Progress in microRNA delivery. J Control Release 172:962-974
140. Piao L, Zhang M, Datta J, Xie X, Su T, Li H, Teknos TN, Pan Q (2012) Lipid-based nanoparticle delivery of Pre-miR-107 inhibits the tumorigenicity of head and neck squamous cell carcinoma. Mol Ther 20:1261-1269
141. Babar IA, Cheng CJ, Booth CJ, Liang X, Weidhaas JB, Saltzman WM, Slack FJ (2012) Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma. Proc Natl Acad Sci U S A 109:E1695-E1704
142. Ohno S, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyama N, Fujita K, Mizutani T, Ohgi T, Ochiya T et al (2013) Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther 21:185-191
143. van Miltenburg MH, Jonkers J (2012) Using genetically engineered mouse models to validate candidate cancer genes and test new therapeutic approaches. Curr Opin Genet Dev 22:21-27
144. Landis MD, Lehmann BD, Pietenpol JA, Chang JC (2013) Patient-derived breast tumor xenografts facilitating personalized cancer therapy. Breast Cancer Res 15:201
145. Zhang J, Ma L (2012) MicroRNA control of epithelial-mesenchymal transition and metastasis. Cancer Metastasis Rev 31:653-662
146. Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL, Wahl GM (2006) Cancer stem cells-perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66:9339-9344
147. Horvat EA, Zhang JD, Uhlmann S, Sahin O, Zweig KA (2013) A network-based method to assess the statistical significance of mild co-regulation effects. PLoS ONE 8:e73413
148. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 105:10513-10518
149. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997-1006
150. Kitamura K, Seike M, Okano T, Matsuda K, Miyanaga A, Mizutani H, Noro R, Minegishi Y, Kubota K, Gemma A (2013) MiR-134/487b/655 Cluster Regulates TGF-beta-induced Epithelial-Mesenchymal Transition and Drug Resistance to Gefitinib by Targeting MAGI2 in Lung Adenocarcinoma Cells. Mol Cancer Ther. doi: 10.1158/1535-7163.MCT-13-0448
151. Chang CJ, Hsu CC, Chang CH, Tsai LL, Chang YC, Lu SW, Yu CH, Huang HS, Wang JJ, Tsai CH et al (2011) Let-7d functions as novel regulator of epithelial-mesenchymal transition and chemoresistant property in oral cancer. Oncol Rep 26:1003-1010
152. Vaira V, Faversani A, Martin NM, Garlick DS, Ferrero S, Nosotti M, Kissil JL, Bosari S, Altieri DC (2013) Regulation of lung cancer metastasis by Klf4-Numb-like signaling. Cancer Res 73:2695-2705
153. Ren D, Wang M, Guo W, Zhao X, Tu X, Huang S, Zou X, Peng X (2013) Wild-type p53 suppresses the epithelial-mesenchymal transition and stemness in PC-3 prostate cancer cells by modulating miR145. Int J Oncol 42:1473-1481
154. Han M, Wang Y, Liu M, Bi X, Bao J, Zeng N, Zhu Z, Mo Z, Wu C, Chen X (2012) MiR-21 regulates epithelial-mesenchymal transition phenotype and hypoxia-inducible factor-1alpha expression in third-sphere forming breast cancer stem cell-like cells. Cancer Sci 103:1058-1064
155. Fan X, Chen X, Deng W, Zhong G, Cai Q, Lin T (2013) Up-regulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression. BMC Cancer 13:61
156. Chiou GY, Cherng JY, Hsu HS, Wang ML, Tsai CM, Lu KH, Chien Y, Hung SC, Chen YW, Wong CI et al (2012) Cationic polyurethanes-short branch PEI-mediated delivery of Mir145 inhibited epithelial-mesenchymal transdifferentiation and cancer stem-like properties and in lung adenocarcinoma. J Control Release 159:240-250
157. Guttilla IK, Phoenix KN, Hong X, Tirnauer JS, Claffey KP, White BA (2012) Prolonged mammosphere culture of MCF-7 cells induces an EMT and repression of the estrogen receptor by microRNAs. Breast Cancer Res Treat 132:75-85
158. Yang YP, Chien Y, Chiou GY, Cherng JY, Wang ML, Lo WL, Chang YL, Huang PI, Chen YW, Shih YH et al (2012) Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI. Biomaterials 33:1462-1476
159. Jeon HM, Sohn YW, Oh SY, Kim SH, Beck S, Kim S, Kim H (2011) ID4 imparts chemoresistance and cancer stemness to glioma cells by derepressing miR-9-mediated suppression of SOX2. Cancer Res 71:3410-3421
160. Cheng W, Liu T, Wan X, Gao Y, Wang H (2012) MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells. FEBS J 279:2047-2059
161. Yu CC, Chen YW, Chiou GY, Tsai LL, Huang PI, Chang CY, Tseng LM, Chiou SH, Yen SH, Chou MY et al (2011) MicroRNA let-7a represses chemoresistance and tumourigenicity in head and neck cancer via stem-like properties ablation. Oral Oncol 47:202-210
162. Nakajima G, Hayashi K, Xi Y, Kudo K, Uchida K, Takasaki K, Yamamoto M, Ju J (2006) Non-coding MicroRNAs hsa-let-7 g and hsa-miR-181b are Associated with Chemoresponse to S-1 in Colon Cancer. Cancer Genomics Proteomics 3:317-324
163. Tong JL, Zhang CP, Nie F, Xu XT, Zhu MM, Xiao SD, Ran ZH (2011) MicroRNA 506 regulates expression of PPAR alpha in hydroxycamptothecin-resistant human colon cancer cells. FEBS Lett 585:3560-3568
164. Ragusa M, Majorana A, Statello L, Maugeri M, Salito L, Barbagallo D, Guglielmino MR, Duro LR, Angelica R, Caltabiano R (2010) Specific alterations of microRNA transcriptome and global network structure in colorectal carcinoma after cetuximab treatment. Mol Cancer Ther 9:3396-3409
165. Ru P, Steele R, Hsueh EC, Ray RB (2011) Anti-miR-203 Upregulates SOCS3 Expression in Breast Cancer Cells and Enhances Cisplatin Chemosensitivity. Genes Cancer 2:720-727
166. Kovalchuk O, Filkowski J, Meservy J, Ilnytskyy Y, Tryndyak VP, Chekhun VF, Pogribny IP (2008) Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol Cancer Ther 7:2152-2159
167. Kalinowski FC, Giles KM, Candy PA, Ali A, Ganda C, Epis MR, Webster RJ, Leedman PJ (2012) Regulation of epidermal growth factor receptor signaling and erlotinib sensitivity in head and neck cancer cells by miR-7. PLoS ONE 7:e47067
168. Chen G, Umelo IA, Lv S, Teugels E, Fostier K, Kronenberger P, Dewaele A, Sadones J, Geers C, De Greve J (2013) miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. PLoS ONE 8:e60317
169. Masri S, Liu Z, Phung S, Wang E, Yuan YC, Chen S (2010) The role of microRNA-128a in regulating TGFbeta signaling in letrozole-resistant breast cancer cells. Breast Cancer Res Treat 124:89-99
170. Pan YZ, Morris ME, Yu AM (2009) MicroRNA-328 negatively regulates the expression of breast cancer resistance protein (BCRP/ABCG2) in human cancer cells. Mol Pharmacol 75:1374-1379
171. Sorrentino A, Liu CG, Addario A, Peschle C, Scambia G, Ferlini C (2008) Role of microRNAs in drug-resistant ovarian cancer cells. Gynecol Oncol 111:478-486
172. Costa PM, Cardoso AL, Nobrega C, Pereira de Almeida LF, Bruce JN, Canoll P, Pedroso de Lima MC (2013) MicroRNA-21 silencing enhances the cytotoxic effect of the antiangiogenic drug sunitinib in glioblastoma. Hum Mol Genet 22:904-918
173. Berkers J, Govaere O, Wolter P, Beuselinck B, Schoffski P, van Kempen LC, Albersen M, Van den Oord J, Roskams T, Swinnen J et al (2013) 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 189:1930-1938
174. Zhu H, Wu H, Liu X, Evans BR, Medina DJ, Liu CG, Yang JM (2008) Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem Pharmacol 76:582-588
175. Chou J, Lin JH, Brenot A, Kim JW, Provot S, Werb Z (2013) GATA3 suppresses metastasis and modulates the tumour microenvironment by regulating microRNA-29b expression. Nat Cell Biol 15:201-213
176. Fang JH, Zhou HC, Zeng C, Yang J, Liu Y, Huang X, Zhang JP, Guan XY, Zhuang SM (2011) MicroRNA-29b suppresses tumor angiogenesis, invasion, and metastasis by regulating matrix metalloproteinase 2 expression. Hepatology 54:1729-1740
177. Kumarswamy R, Mudduluru G, Ceppi P, Muppala S, Kozlowski M, Niklinski J, Papotti M, Allgayer H (2012) MicroRNA-30a inhibits epithelial-to-mesenchymal transition by targeting Snai1 and is downregulated in non-small cell lung cancer. Int J Cancer 130:2044-2053
178. Lin CW, Chang YL, Chang YC, Lin JC, Chen CC, Pan SH, Wu CT, Chen HY, Yang SC, Hong TM et al (2013) MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1. Nat Commun 4:1877
179. Yigit MV, Ghosh SK, Kumar M, Petkova V, Kavishwar A, Moore A, Medarova Z (2013) Context-dependent differences in miR-10b breast oncogenesis can be targeted for the prevention and arrest of lymph node metastasis. Oncogene 32:1530-1538
180. Penna E, Orso F, Cimino D, Vercellino I, Grassi E, Quaglino E, Turco E, Taverna D (2013) miR-214 coordinates melanoma progression by upregulating ALCAM through TFAP2 and miR-148b downmodulation. Cancer Res 73:4098-4111