Non-small-cell lung cancer and miRNAs: Novel biomarkers and promising tools for treatment

Clinical Science

Volumn 128, Issue 10, 2015, Pages 619-634

  Feng, Bing ^a   Zhang, Kai ^a   Wang, Rui ^a   Chen, Longbang ^a  

^a NANJING UNIVERSITY   (China)

Author keywords

Diagnosis; Individualized treatment; MiRNA; Non small cell lung cancer (NSCLC); Post transcriptional regulation; Prognosis

Indexed keywords

BIOLOGICAL MARKER; CISPLATIN; DNA METHYLTRANSFERASE 3A; DNA METHYLTRANSFERASE 3B; DOCETAXEL; ERLOTINIB; GEFITINIB; MICRORNA; MICRORNA 100; MICRORNA 126; MICRORNA 141; MICRORNA 182; MICRORNA 200; MICRORNA 200A; MICRORNA 200B; MICRORNA 221; MICRORNA 222; MICRORNA 449A; MICRORNA 449B; MICRORNA 449C; MITOGEN ACTIVATED PROTEIN KINASE; NAVELBINE; PACLITAXEL; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; PUMA PROTEIN; RIBONUCLEASE III; RNA POLYMERASE II; TISSUE INHIBITOR OF METALLOPROTEINASE 3; UNCLASSIFIED DRUG; UNINDEXED DRUG; TUMOR MARKER;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BIOGENESIS; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER RESISTANCE; CANCER THERAPY; CELL CYCLE ARREST; CELL CYCLE REGULATION; CELL PROLIFERATION; DRUG TARGETING; EPITHELIAL MESENCHYMAL TRANSITION; GENETIC POLYMORPHISM; HUMAN; METASTASIS; MOLECULARLY TARGETED THERAPY; NON SMALL CELL LUNG CANCER; NONHUMAN; PRIORITY JOURNAL; PROTEIN RNA BINDING; REVIEW; RNA PROCESSING; TRANSCRIPTION REGULATION; TUMOR SUPPRESSOR GENE; BIOSYNTHESIS; CARCINOMA, NON-SMALL-CELL LUNG; DIAGNOSTIC USE; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENETICS; METABOLISM; PATHOPHYSIOLOGY; PERSONALIZED MEDICINE; PROCEDURES; SINGLE NUCLEOTIDE POLYMORPHISM; TRENDS;

CARCINOMA, NON-SMALL-CELL LUNG; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INDIVIDUALIZED MEDICINE; MICRORNAS; POLYMORPHISM, SINGLE NUCLEOTIDE; TUMOR MARKERS, BIOLOGICAL;

EID: 84928936439     PISSN: 01435221     EISSN: 14708736     Source Type: Journal    
DOI: 10.1042/CS20140530     Document Type: Review

References (170)

1. Minna, J.D., Roth, J.A. and Gazdar, A.F. (2002) Focus on lung cancer. Cancer Cell 1, 49-52
2. Siegel, R., Ma, J., Zou, Z. and Jemal, A. (2014) Cancer statistics, 2014. CA Cancer J. Clin. 64, 9-29
3. Bartel, D.P. (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297
4. Winter, J., Jung, S., Keller, S., Gregory, R.I. and Diederichs, S. (2009) Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat. Cell Biol. 11, 228-234
5. Ørom, U.A., Nielsen, F.C. and Lund, A.H. (2008) MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation. Mol. Cell 30, 460-471
6. Tay, Y., Zhang, J., Thomson, A.M., Lim, B. and Rigoutsos, I. (2008) MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455, 1124-1128
7. Eiring, A.M., Harb, J.G., Neviani, P., Garton, C., Oaks, J.J., Spizzo, R., Liu, S., Schwind, S., Santhanam, R., Hickey, C.J. et al. (2010) miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell 140, 652-665
8. Egger, G., Liang, G., Aparicio, A. and Jones, P.A. (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429, 457-463
9. Calin, G.A., Dumitru, C.D., Shimizu, M., Bichi, R., Zupo, S., Noch, E., Aldler, H., Rattan, S., Keating, M., Rai, K. et al. (2002) Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc. Natl. Acad. Sci. U.S.A. 99, 15524-15529
10. Calin, G.A., Sevignani, C., Dumitru, C.D., 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
11. Lujambio, A., Ropero, S., Ballestar, E., Fraga, M.F., Cerrato, C., Setién, F., Casado, S., Suarez-Gauthier, A., Sanchez-Cespedes, M., Git, A. et al. (2007) Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res. 67, 1424-1429
12. Lujambio, A., Calin, G.A., Villanueva, A., Ropero, S., Sánchez-Céspedes, M., Blanco, D., Montuenga, L.M., Rossi, S., Nicoloso, M.S., Faller, W.J. et al. (2008) A microRNA DNA methylation signature for human cancer metastasis. Proc. Natl. Acad. Sci. U.S.A. 105, 13556-13561
13. Heller, G., Weinzierl, M., Noll, C., Babinsky, V., Ziegler, B., Altenberger, C., Minichsdorfer, C., Lang, G., Döme, B., End-Pfützenreuter, A. et al. (2012) Genome-wide miRNA expression profiling identifies miR-9-3 and miR-193a as targets for DNA methylation in non-small cell lung cancers. Clin. Cancer Res. 18, 1619-1629
14. Wang, Z., Chen, Z., Gao, Y., Li, N., Li, B., Tan, F., Tan, X., Lu, N., Sun, Y., Sun, J. et al. (2011) DNA hypermethylation of microRNA-34b/c has prognostic value for stage I non-small cell lung cancer. Cancer Biol. Ther. 11, 490-496
15. Incoronato, M., Urso, L., Portela, A., Laukkanen, M.O., Soini, Y., Quintavalle, C., Keller, S., Esteller, M. and Condorelli, G. (2011) Epigenetic regulation of miR-212 expression in lung cancer. PLoS One 6, e27722
16. Chen, D.Q., Pan, B.Z., Huang, J.Y., Zhang, K., Cui, S.Y., De, W., Wang, R. and Chen, L.B. (2014) HDAC 1/4-mediated silencing of microRNA-200b promotes chemoresistance in human lung adenocarcinoma cells. Oncotarget 5, 3333-3349
17. Sun, G., Yan, J., Noltner, K., Feng, J., Li, H., Sarkis, D.A., Sommer, S.S. and Rossi, J.J. (2009) SNPs in human miRNA genes affect biogenesis and function. RNA 15, 1640-1651
18. Qiu, M.T., Hu, J.W., Ding, X.X., Yang, X., Zhang, Z., Yin, R. and Xu, L. (2012) Hsa-miR-499 rs3746444 polymorphism contributes to cancer risk: a meta-analysis of 12 studies. PLoS One 7, e50887
19. Guo, J., Jin, M., Zhang, M. and Chen, K. (2012) A genetic variant in miR-196a2 increased digestive system cancer risks: a meta-analysis of 15 case-control studies. PLoS One 7, e30585
20. Chin, L.J., Ratner, E., Leng, S., Zhai, R., Nallur, S., Babar, I., Muller, R.U., Straka, E., Su, L., Burki, E.A. et al. (2008) A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk. Cancer Res. 68, 8535-8540
21. He, L., He, X., Lim, L.P., de Stanchina, E., Xuan, Z., Liang, Y., Xue, W., Zender, L., Magnus, J., Ridzon, D. et al. (2007) A microRNA component of the p53 tumour suppressor network. Nature 447, 1130-1134
22. O'Donnell, K.A., Wentzel, E.A., Zeller, K.I., Dang, C.V. and Mendell, J.T. (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435, 839-843
23. Davis, B.N., Hilyard, A.C., Nguyen, P.H., Lagna, G. and Hata, A. (2010) Smad proteins bind a conserved RNA sequence to promote microRNA maturation by Drosha. Mol. Cell 39, 373-384
24. Tili, E., Michaille, J.J., Liu, C.G., Alder, H., Taccioli, C., Volinia, S., Calin, G.A. and Croce, C.M. (2010) GAM/ZFp/ZNF512B is central to a gene sensor circuitry involving cell-cycle regulators, TGF{beta} effectors, Drosha and microRNAs with opposite oncogenic potentials. Nucleic Acids Res. 38, 7673-7688
25. Qian, B., Katsaros, D., Lu, L., Preti, M., Durando, A., Arisio, R., Mu, L. and Yu, H. (2009) High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-beta1. Breast Cancer Res. Treat. 117, 131-140
26. Ahn, S.M., Cha, J.Y., Kim, J., Kim, D., Trang, H.T., Kim, Y.M., Cho, Y.H., Park, D. and Hong, S. (2012) Smad3 regulates E-cadherin via miRNA-200 pathway. Oncogene 31, 3051-3059
27. Dogar, A.M., Towbin, H. and Hall, J. (2011) Suppression of latent transforming growth factor (TGF)-beta1 restores growth inhibitory TGF-beta signaling through microRNAs. J. Biol. Chem. 286, 16447-16458
28. Trabucchi, M., Briata, P., Garcia-Mayoral, M., Haase, A.D., Filipowicz, W., Ramos, A., Gherzi, R. and Rosenfeld, M.G. (2009) The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature 459, 1010-1014
29. Guil, S. and Cáceres, J.F. (2007) The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a. Nat. Struct. Mol. Biol. 14, 591-596
30. Michlewski, G., Guil, S., Semple, C.A. and Cáceres, J.F. (2008) Posttranscriptional regulation of miRNAs harboring conserved terminal loops. Mol. Cell 32, 383-393
31. Melo, S.A., Moutinho, C., Ropero, S., Calin, G.A., Rossi, S., Spizzo, R., Fernandez, A.F., Davalos, V., Villanueva, A., Montoya, G. et al. (2010) A genetic defect in exportin-5 traps precursor microRNAs in the nucleus of cancer cells. Cancer Cell 18, 303-315
32. Salmena, L., Poliseno, L., Tay, Y., Kats, L. and Pandolfi, P.P. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146, 353-358
33. Wang, J., Liu, X., Wu, H., Ni, P., Gu, Z., Qiao, Y., Chen, N., Sun, F. and Fan, Q. (2010) CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res. 38, 5366-5383
34. Fan, M., Li, X., Jiang, W., Huang, Y., Li, J. and Wang, Z. (2013) A long non-coding RNA, PTCSC3, as a tumor suppressor and a target of miRNAs in thyroid cancer cells. Exp. Ther. Med. 5, 1143-1146
35. Yang, J., Li, T., Gao, C., Lv, X., Liu, K., Song, H., Xing, Y. and Xi, T. (2014) FOXO1 3'UTR functions as a ceRNA in repressing the metastases of breast cancer cells via regulating miRNA activity. FEBS. Lett. 588, 3218-3124
36. Davis, B.N., Hilyard, A.C., Lagna, G. and Hata, A. (2008) SMAD proteins control DROSHA-mediated microRNA maturation. Nature 454, 56-61
37. Kedde, M., van, Kouwenhove, M., Zwart, W., Oude, Vrielink, J.A., Elkon, R. and Agami, R. (2010) A Pumilio-induced RNA structure switch in p27-3' UTR controls miR-221 and miR-222 accessibility. Nat. Cell Biol. 12, 1014-1020
38. Miles, W.O., Tschöp, K., Herr, A., Ji, J.Y. and Dyson, N.J. (2012) Pumilio facilitates miRNA regulation of the E2F3 oncogene. Genes Dev. 26, 356-368
39. Johnson, C.D., 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
40. Tokumaru, S., Suzuki, M., Yamada, H., Nagino, M. and Takahashi, T. (2008) let-7 regulates Dicer expression and constitutes a negative feedback loop. Carcinogenesis 29, 2073-2077
41. Esquela-Kerscher, A., Trang, P., Wiggins, J.F., Patrawala, L., Cheng, A., Ford, L., Weidhaas, J.B., Brown, D., Bader, A.G. and Slack, F.J. (2008) The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle 7, 759-764
42. Yanaihara, N., Caplen, N., Bowman, E., Seike, M., Kumamoto, K., Yi, M., Stephens, R.M., Okamoto, A., Yokota, J., Tanaka, T. et al. (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9, 189-198
43. Wang, X., Dong, K., Gao, P., Long, M., Lin, F., Weng, Y., Ouyang, Y., Ren, J. and Zhang, H. (2013) microRNA-34a sensitizes lung cancer cell lines to DDP treatment independent of p53 status. Cancer Biother. Radiopharm. 28, 45-50
44. Shi, Y., Liu, C., Liu, X., Tang, D.G. and Wang, J. (2014) The microRNA miR-34a inhibits non-small cell lung cancer (NSCLC) growth and the CD44hi stem-like NSCLC cells. PLoS One 9, e90022
45. Bommer, G.T., Gerin, I., Feng, Y., Kaczorowski, A.J., Kuick, R., Love, R.E., Zhai, Y., Giordano, T.J., Qin, Z.S., Moore, B.B. et al. (2007) p53-mediated activation of miRNA34 candidate tumor suppressor genes. Curr. Biol. 17, 1298-1307
46. Lizé, M., Pilarski, S. and Dobbelstein, M. (2010) E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis. Cell Death Differ. 17, 452-458
47. Jeon, H.S., Lee, S.Y., Lee, E.J., Yun, S.C., Cha, E.J., Choi, E., Na, M.J., Park, J.Y., Kang, J. and Son, J.W. (2012) Combining microRNA-449a/b with a HDAC inhibitor has a synergistic effect on growth arrest in lung cancer. Lung Cancer 76, 171-176
48. Bandi, N., Zbinden, S., Gugger, M., Arnold, M., Kocher, V., Hasan, L., Kappeler, A., Brunner, T. and Vassella, E. (2009) 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. 69, 5553-5559
49. Bandi, N. and Vassella, E. (2011) miR-34a and miR-15a/16 are co-regulated in non-small cell lung cancer and control cell cycle progression in a synergistic and Rb-dependent manner. Mol. Cancer 10, 55
50. Gregory, P.A., Bert, A.G., Paterson, E.L., Barry, S.C., Tsykin, A., Farshid, G., Vadas, M.A., Khew-Goodall, Y. and Goodall, G.J. (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat. Cell Biol. 10, 593-601
51. Hurteau, G.J., Carlson, J.A., Spivack, S.D. and Brock, G.J. (2007) Overexpression of the microRNA hsa-miR-200c leads to reduced expression of transcription factor 8 and increased expression of E-cadherin. Cancer Res. 67, 7972-7976
52. Ceppi, P., Mudduluru, G., Kumarswamy, R., Rapa, I., Scagliotti, G.V., Papotti, M. and 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
53. Shimono, Y., Zabala, M., Cho, R.W., Lobo, N., Dalerba, P., Qian, D., Diehn, M., Liu, H., Panula, S.P., Chiao, E. et al. (2009) Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138, 592-603
54. Kopp, F., Wagner, E. and Roidl, A. (2014) The proto-oncogene KRAS is targeted by miR-200c. Oncotarget 5, 185-195
55. Rui, W., Bing, F., Hai-Zhu, S., Wei, D. and Long-Bang, C. (2010) Identification of microRNA profiles in docetaxel-resistant human non-small cell lung carcinoma cells (SPC-A1). J. Cell. Mol. Med. 14, 206-214
56. Feng, B., Wang, R., Song, H.Z. and Chen, L.B. (2012) MicroRNA-200b reverses chemoresistance of docetaxel-resistant human lung adenocarcinoma cells by targeting E2F3. Cancer 118, 3365-3376
57. Choi, Y.C., Yoon, S., Jeong, Y., Yoon, J. and Baek, K. (2011) Regulation of vascular endothelial growth factor signaling by miR-200b. Mol. Cells 32, 77-82
58. Wang, R., Wang, Z.X., Yang, J.S., Pan, X., De, W. and Chen, L.B. (2011) MicroRNA-451 functions as a tumor suppressor in human non-small cell lung cancer by targeting ras-related protein 14 (RAB14). Oncogene 30, 2644-2658
59. Fabbri, M., Garzon, R., Cimmino, A., Liu, Z., Zanesi, N., Callegari, E., Liu, S., Alder, H., Costinean, S., Fernandez-Cymering, C. et al. (2007) MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc. Natl. Acad. Sci. U.S.A. 104, 15805-15810
60. Gebeshuber, C.A., Zatloukal, K. and Martinez, J. (2009) miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis. EMBO Rep. 10, 400-405
61. Mott, J.L., Kobayashi, S., Bronk, S.F. and Gores, G.J. (2007) mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene 26, 6133-6140
62. Wang, X.C., Du, L.Q., Tian, L.L., Wu, H.L., Jiang, X.Y., Zhang, H., Li, D.G., Wang, Y.Y., Wu, H.Y., She, Y. et al. (2011) Expression and function of miRNA in postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer. Lung Cancer 72, 92-99
63. Liu, B., Peng, X.C., Zheng, X.L., Wang, J. and Qin, Y.W. (2009) MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. Lung Cancer 66, 169-175
64. Sun, Y., Bai, Y., Zhang, F., Wang, Y., Guo, Y. and Guo, L. (2010) miR-126 inhibits non-small cell lung cancer cells proliferation by targeting EGFL7. Biochem. Biophys. Res. Commun. 391, 1483-1489
65. Zhang, J.G., Guo, J.F., Liu, D.L., Liu, Q. and Wang, J.J. (2011) MicroRNA-101 exerts tumor-suppressive functions in non-small cell lung cancer through directly targeting enhancer of zeste homolog 2. J. Thorac. Oncol. 6, 671-678
66. Luo, L., Zhang, T., Liu, H., Lv, T., Yuan, D., Yao, Y., Lv, Y. and Song, Y. (2012) MiR-101 and Mcl-1 in non-small-cell lung cancer: expression profile and clinical significance. Med. Oncol. 29, 1681-1686
67. Sun, Y., Fang, R., Li, C., Li, L., Li, F., Ye, X. and Chen, H. (2010) Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro. Biochem. Biophys. Res. Commun. 396, 501-507
68. Feng, S., Cong, S., Zhang, X., Bao, X., Wang, W., Li, H., Wang, Z., Wang, G., Xu, J., Du, B. et al. (2011) MicroRNA-192 targeting retinoblastoma 1 inhibits cell proliferation and induces cell apoptosis in lung cancer cells. Nucleic Acids Res. 39, 6669-6678
69. Incoronato, M., Garofalo, M., Urso, L., Romano, G., Quintavalle, C., Zanca, C., Iaboni, M., Nuovo, G., Croce, C.M. and Condorelli, G. (2010) miR-212 increases tumor necrosis factor-related apoptosis-inducing ligand sensitivity in non-small cell lung cancer by targeting the antiapoptotic protein PED. Cancer Res. 70, 3638-3646
70. Wu, D.W., Cheng, Y.W., Wang, J., Chen, C.Y. and Lee, H. (2010) Paxillin predicts survival and relapse in non-small cell lung cancer by microRNA-218 targeting. Cancer Res. 70, 10392-10401
71. Wu, J., Qian, J., Li, C., Kwok, L., Cheng, F., Liu, P., Perdomo, C., Kotton, D., Vaziri, C., Anderlind, C. et al. (2010) miR-129 regulates cell proliferation by downregulating Cdk6 expression. Cell Cycle 9, 1809-1818
72. Du, B., Wang, Z., Zhang, X., Feng, S., Wang, G., He, J. and Zhang, B. (2014) MicroRNA-545 suppresses cell proliferation by targeting cyclin D1 and CDK4 in lung cancer cells. PLoS One 9, e88022
73. Mendell, J.T. (2008) miRiad roles for the miR-17-92 cluster in development and disease. Cell 133, 217-222
74. Lewis, B.P., Shih, I.H., Jones-Rhoades, M.W., Bartel, D.P. and Burge, C.B. (2003) Prediction of mammalian microRNA targets. Cell 115, 787-798
75. Taguchi, A., Yanagisawa, K., Tanaka, M., Cao, K., Matsuyama, Y., Goto, H. and Takahashi, T. (2008) Identification of hypoxia-inducible factor-1 alpha as a novel target for miR-17-92 microRNA cluster. Cancer Res. 68, 5540-5545
76. Ebi, H., Sato, T., Sugito, N., Hosono, Y., Yatabe, Y., Matsuyama, Y., Yamaguchi, T., Osada, H., Suzuki, M. and Takahashi, T. (2009) Counterbalance between RB inactivation and miR-17-92 overexpression in reactive oxygen species and DNA damage induction in lung cancers. Oncogene 28, 3371-3379
77. Garofalo, M., Di Leva, G., Romano, G., Nuovo, G., Suh, S.S., Ngankeu, A., Taccioli, C., Pichiorri, F., Alder, H., Secchiero, P. et al. (2009) miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell 16, 498-509
78. Garofalo, M., Romano, G., Di Leva, G., Nuovo, G., Jeon, Y.J., Ngankeu, A., Sun, J., Lovat, F., Alder, H., Condorelli, G. et al. (2011) EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers. Nat. Med. 18, 74-82
79. Zhang, C., Zhang, J., Zhang, A., Wang, Y., Han, L., You, Y., Pu, P. and Kang, C. (2010) PUMA is a novel target of miR-221/222 in human epithelial cancers. Int. J. Oncol. 37, 1621-1626
80. Volinia, S., Calin, G.A., Liu, C.G., Ambs, S., Cimmino, A., Petrocca, F., Visone, R., Iorio, M., Roldo, C., Ferracin, M. et al. (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc. Natl. Acad. Sci. U.S.A. 103, 2257-2261
81. Seike, M., Goto, A., Okano, T., Bowman, E.D., Schetter, A.J., Horikawa, I., Mathe, E.A., Jen, J., Yang, P., Sugimura, H. et al. (2009) MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers. Proc. Natl. Acad. Sci. U.S.A. 106, 12085-12090
82. Zhang, J.G., Wang, J.J., Zhao, F., Liu, Q., Jiang, K. and Yang, G.H. (2010) MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). Clin. Chim. Acta 411, 846-852
83. Hatley, M.E., Patrick, D.M., Garcia, M.R., Richardson, J.A., Bassel-Duby, R., van Rooij, E. and Olson, E.N. (2010) Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21. Cancer Cell 18, 282-293
84. Liu, X., Sempere, L.F., Ouyang, H., Memoli, V.A., Andrew, A.S., Luo, Y., Demidenko, E., Korc, M., Shi, W., Preis, M. et al. (2010) MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. J. Clin. Invest. 120, 1298-1309
85. Liu, L., Jiang, Y., Zhang, H., Greenlee, A.R. and Han, Z. (2010) Overexpressed miR-494 down-regulates PTEN gene expression in cells transformed by anti-benzo(a)pyrene-trans-7, 8-dihydrodiol-9, 10-epoxide. Life Sci. 86, 192-198
86. Cao, G., Huang, B., Liu, Z., Zhang, J., Xu, H., Xia, W., Li, J., Li, S., Chen, L., Ding, H. et al. (2010) Intronic miR-301 feedback regulates its host gene, ska2, in A549 cells by targeting MEOX2 to affect ERK/CREB pathways. Biochem. Biophys. Res. Commun. 396, 978-982
87. Duncavage, E., Goodgame, B., Sezhiyan, A., Govindan, R. and Pfeifer, J. (2010) Use of microRNA expression levels to predict outcomes in resected stage I non-small cell lung cancer. J. Thorac. Oncol. 5, 1755-1763
88. Rai, K., Takigawa, N., Ito, S., Kashihara, H., Ichihara, E., Yasuda, T., Shimizu, K., Tanimoto, M. and Kiura, K. (2011) Liposomal delivery of MicroRNA-7-expressing plasmid overcomes epidermal growth factor receptor tyrosine kinase inhibitor-resistance in lung cancer cells. Mol. Cancer Ther. 10, 1720-1727
89. Xiong, S., Zheng, Y., Jiang, P., Liu, R., Liu, X. and Chu, Y. (2011) MicroRNA-7 inhibits the growth of human non-small cell lung cancer A549 cells through targeting BCL-2. Int. J. Biol. Sci. 7, 805-814
90. Webster, R.J., Giles, K.M., Price, K.J., Zhang, P.M., Mattick, J.S. and Leedman, P.J. (2009) Regulation of epidermal growth factor receptor signaling in human cancer cells by microRNA-7. J. Biol. Chem. 284, 5731-5741
91. Chou, Y.T., Lin, H.H., Lien, Y.C., Wang, Y.H., Hong, C.F., Kao, Y.R., Lin, S.C., Chang, Y.C., Lin, S.Y., Chen, S.J. et al. (2010) EGFR promotes lung tumorigenesis by activating miR-7 through a Ras/ERK/Myc pathway that targets the Ets2 transcriptional repressor ERF. Cancer Res. 70, 8822-8831
92. Myatt, S.S., Wang, J., Monteiro, L.J., Christian, M., Ho, K.K., Fusi, L., Dina, R.E., Brosens, J.J., Ghaem-Maghami, S. and Lam, E.W. (2010) Definition of microRNAs that repress expression of the tumor suppressor gene FOXO1 in endometrial cancer. Cancer Res. 70, 367-377
93. Zhang, L., Liu, T., Huang, Y. and Liu, J. (2011) microRNA-182 inhibits the proliferation and invasion of human lung adenocarcinoma cells through its effect on human cortical actin-associated protein. Int. J. Mol. Med. 28, 381-388
94. Wang, G., Mao, W. and Zheng, S. (2008) MicroRNA-183 regulates Ezrin expression in lung cancer cells. FEBS Lett. 582, 3663-3668
95. Zhu, W., Liu, X., He, J., Chen, D., Hunag, Y. and Zhang, Y.K. (2011) Overexpression of members of the microRNA-183 family is a risk factor for lung cancer: a case control study. BMC Cancer 11, 393
96. Lu, J., Getz, G., Miska, E.A., Alvarez-Saavedra, E., Lamb, J., Peck, D., Sweet-Cordero, A., Ebert, B.L., Mak, R.H., Ferrando, A.A. et al. (2005) MicroRNA expression profiles classify human cancers. Nature 435, 834-838
97. Raponi, M., Dossey, L., Jatkoe, T., Wu, X., Chen, G., Fan, H. and Beer, D.G. (2009) MicroRNA classifiers for predicting prognosis of squamous cell lung cancer. Cancer Res. 69, 5776-5783
98. Arroyo, J.D., Chevillet, J.R., Kroh, E.M., Ruf, I.K., Pritchard, C.C., Gibson, D.F., Mitchell, P.S., Bennett, C.F., Pogosova-Agadjanyan, E.L., Stirewalt, D.L. et al. (2011) Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc. Natl. Acad. Sci. U.S.A. 108, 5003-5008
99. Shen, J., Todd, N.W., Zhang, H., Yu, L., Lingxiao, X., Mei, Y., Guarnera, M., Liao, J., Chou, A., Lu, C.L. et al. (2011) Plasma microRNAs as potential biomarkers for non-small-cell lung cancer. Lab. Invest. 91, 579-587
100. Hu, Z., Chen, X., Zhao, Y., Tian, T., Jin, G., Shu, Y., Chen, Y., Xu, L., Zen, K., Zhang, C. et al. (2010) Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J. Clin. Oncol. 28, 1721-1726
101. Xie, Y., Todd, N.W., Liu, Z., Zhan, M., Fang, H., Peng, H., Alattar, M., Deepak, J., Stass, S.A. and Jiang, F. (2010) Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer. Lung Cancer 67, 170-176
102. Park, N.J., Zhou, H., Elashoff, D., Henson, B.S., Kastratovic, D.A., Abemayor, E. and Wong, D.T. (2009) Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin. Cancer Res. 15, 5473-5477
103. Hanke, M., Hoefig, K., Merz, H., Feller, A.C., Kausch, I., Jocham, D., Warnecke, J.M. and Sczakiel, G. (2010) A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol. Oncol. 28, 655-661
104. Kosaka, N., Izumi, H., Sekine, K. and Ochiya, T. (2010) microRNA as a new immune-regulatory agent in breast milk. Silence 1, 7
105. 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
106. Heegaard, N.H., Schetter, A.J., Welsh, J.A., Yoneda, M., Bowman, E.D. and Harris, C.C. (2012) Circulating micro-RNA expression profiles in early stage nonsmall cell lung cancer. Int. J. Cancer 130, 1378-1386
107. Zheng, D., Haddadin, S., Wang, Y., Gu, L.Q., Perry, M.C., Freter, C.E. and Wang, M.X. (2011) Plasma microRNAs as novel biomarkers for early detection of lung cancer. Int. J. Clin. Exp. Pathol. 4, 575-586
108. Zhu, W., He, J., Chen, D., Zhang, B., Xu, L., Ma, H., Liu, X., Zhang, Y. and Le, H. (2014) Expression of miR-29c, miR-93, and miR-429 as potential biomarkers for detection of early stage non-small lung cancer. PLoS One 9, e87780
109. Yu, L., Todd, N.W., Xing, L., Xie, Y., Zhang, H., Liu, Z., Fang, H., Zhang, J., Katz, R.L. and Jiang, F. (2010) Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int. J. Cancer 127, 2870-2878
110. Wang, Q., Wang, S., Wang, H., Li, P. and Ma, Z. (2012) MicroRNAs: novel biomarkers for lung cancer diagnosis, prediction and treatment. Exp. Biol. Med. (Maywood) 237, 227-235
111. Xing, L., Todd, N.W., Yu, L., Fang, H. and Jiang, F. (2010) Early detection of squamous cell lung cancer in sputum by a panel of microRNA markers. Mod. Pathol. 23, 1157-1164
112. Tan, X., Qin, W., Zhang, L., Hang, J., Li, B., Zhang, C., Wan, J., Zhou, F., Shao, K., Sun, Y. et al. (2011) A 5-microRNA signature for lung squamous cell carcinoma diagnosis and hsa-miR-31 for prognosis. Clin. Cancer Res. 17, 6802-6811
113. Molina-Pinelo, S., Gutiérrez, G., Pastor, M.D., Hergueta, M., Moreno-Bueno, G., García-Carbonero, R., Nogal, A., Suárez, R., Salinas, A., Pozo-Rodríguez, F. et al. (2014) MicroRNA-dependent regulation of transcription in non-small cell lung cancer. PLoS One 9, e90524
114. Du, L., Schageman, J.J., Girard, L., Hammond, S.M., Minna, J.D., Gazdar, A.F. and Pertsemlidis, A. (2010) MicroRNA expression distinguishes SCLC from NSCLC lung tumor cells and suggests a possible pathological relationship between SCLCs and NSCLCs. J. Exp. Clin. Cancer Res. 29, 75
115. Gilad, S., Lithwick-Yanai, G., Barshack, I., Benjamin, S., Krivitsky, I., Edmonston, T.B., Bibbo, M., Thurm, C., Horowitz, L., Huang, Y. et al. (2012) Classification of the four main types of lung cancer using a microRNA-based diagnostic assay. J. Mol. Diagn. 14, 510-517
116. Takamizawa, J., Konishi, H., Yanagisawa, K., Tomida, S., Osada, H., Endoh, H., Harano, T., Yatabe, Y., Nagino, M., Nimura, Y. et al. (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 64, 3753-3756
117. Gallardo, E., Navarro, A., Viñolas, N., Marrades, R.M., Diaz, T., Gel, B., Quera, A., Bandres, E., Garcia-Foncillas, J., Ramirez, J. et al. (2009) miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer. Carcinogenesis 30, 1903-1909
118. Võsa, U., Vooder, T., Kolde, R., Fischer, K., Välk, K., Tõnisson, N., Roosipuu, R., Vilo, J., Metspalu, A. and Annilo, T. (2011) Identification of miR-374a as a prognostic marker for survival in patients with early-stage nonsmall cell lung cancer. Genes Chromosomes Cancer 50, 812-822
119. Gao, W., Yu, Y., Cao, H., Shen, H., Li, X., Pan, S. and Shu, Y. (2010) Deregulated expression of miR-21, miR-143 and miR-181a in non small cell lung cancer is related to clinicopathologic characteristics or patient prognosis. Biomed. Pharmacother. 64, 399-408
120. Wu, C., Cao, Y., He, Z., He, J., Hu, C., Duan, H. and Jiang, J. (2014) Serum levels of miR-19b and miR-146a as prognostic biomarkers for non-small cell lung cancer. Tohoku. J. Exp. Med. 232, 85-95
121. Huang, J.Y., Cui, S.Y., Chen, Y.T., Song, H.Z., Huang, G.C., Feng, B., Sun, M., De, W., Wang, R. and Chen, L.B. (2013) MicroRNA-650 was a prognostic factor in human lung adenocarcinoma and confers the docetaxel chemoresistance of lung adenocarcinoma cells via regulating Bcl-2/Bax expression. PLoS One 8, e72615
122. Donnem, T., Lonvik, K., Eklo, K., Berg, T., Sorbye, S.W., Al-Shibli, K., Al-Saad, S., Andersen, S., Stenvold, H., Bremnes, R.M. et al. (2011) Independent and tissue-specific prognostic impact of miR-126 in nonsmall cell lung cancer: coexpression with vascular endothelial growth factor-A predicts poor survival. Cancer 117, 3193-3200
123. Navarro, A., Diaz, T., Gallardo, E., Viñolas, N., Marrades, R.M., Gel, B., Campayo, M., Quera, A., Bandres, E., Garcia-Foncillas, J. et al. (2011) Prognostic implications of miR-16 expression levels in resected non-small-cell lung cancer. J. Surg. Oncol. 103, 411-415
124. Fang, L., Du, W.W., Yang, W., Rutnam, Z.J., Peng, C., Li, H., O'Malley, Y.Q., Askeland, R.W., Sugg, S., Liu, M. et al. (2012) MiR-93 enhances angiogenesis and metastasis by targeting LATS2. Cell Cycle 11, 4352-4365
125. Wang, G., Mao, W., Zheng, S. and Ye, J. (2009) Epidermal growth factor receptor-regulated miR-125a-5p-a metastatic inhibitor of lung cancer. FEBS J. 276, 5571-5578
126. Lin, Q., Mao, W., Shu, Y., Lin, F., Liu, S., Shen, H., Gao, W., Li, S. and Shen, D. (2012) A cluster of specified microRNAs in peripheral blood as biomarkers for metastatic non-small-cell lung cancer by stem-loop RT-PCR. J. Cancer Res. Clin. Oncol. 138, 85-93
127. Broderick, J.A. and Zamore, P.D. (2011) MicroRNA therapeutics. Gene Ther. 18, 1104-1110
128. Wiggins, J.F., Ruffino, L., Kelnar, K., Omotola, M., Patrawala, L., Brown, D. and Bader, A.G. (2010) Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res. 70, 5923-5930
129. Li, Y.J., Zhang, Y.X., Wang, P.Y., Chi, Y.L., Zhang, C., Ma, Y., Lv, C.J. and Xie, S.Y. (2012) Regression of A549 lung cancer tumors by anti-miR-150 vector. Oncol. Rep. 27, 129-134
130. Obad, S., dos Santos, C.O., Petri, A., Heidenblad, M., Broom, O., Ruse, C., Fu, C., Lindow, M., Stenvang, J., Straarup, E.M. et al. (2011) Silencing of microRNA families by seed-targeting tiny LNAs. Nat. Genet. 43, 371-378
131. Wang, Q., Zhong, M., Liu, W., Li, J., Huang, J. and Zheng, L. (2011) Alterations of microRNAs in cisplatin-resistant human non-small cell lung cancer cells (A549/DDP). Exp. Lung Res. 37, 427-434
132. Zhang, X., Zhu, J., Xing, R., Tie, Y., Fu, H., Zheng, X. and Yu, B. (2012) miR-513a-3p sensitizes human lung adenocarcinoma cells to chemotherapy by targeting GSTP1. Lung Cancer 77, 488-494
133. Yin, J., Wang, M., Jin, C. and Qi, Q. (2014) miR-101 sensitizes A549 NSCLC cell line to CDDP by activating caspase 3-dependent apoptosis. Oncol. Lett. 7, 461-465
134. Galluzzi, L., Morselli, E., Vitale, I., Kepp, O., Senovilla, L., Criollo, A., Servant, N., Paccard, C., Hupé, P., Robert, T. et al. (2010) miR-181a and miR-630 regulate cisplatin-induced cancer cell death. Cancer Res. 70, 1793-1803
135. Zhang, F., Li, Y., Wu, H., Qi, K., You, J., Li, X., Zu, L., Pan, Z., Wang, Y., Li, Y. et al. (2014) MiR-192 confers cisplatin resistance by targeting Bim in lung cancer. Zhongguo Fei Ai Za Zhi 17, 384-390
136. Wei, J., Gao, W., Zhu, C.J., Liu, Y.Q., Mei, Z., Cheng, T. and Shu, Y.Q. (2011) Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer. Chin. J. Cancer 30, 407-414
137. Gao, W., Lu, X., Liu, L., Xu, J., Feng, D. and Shu, Y. (2012) MiRNA-21: a biomarker predictive for platinum-based adjuvant chemotherapy response in patients with non-small cell lung cancer. Cancer Biol. Ther. 13, 330-340
138. Berghmans, T., Ameye, L., Willems, L., Paesmans, M., Mascaux, C., Lafitte, J.J., Meert, A.P., Scherpereel, A., Cortot, A.B., Cstoth, I. et al. (2013) Identification of microRNA-based signatures for response and survival for non-small cell lung cancer treated with cisplatin-vinorelbine A ELCWP prospective study. Lung Cancer 82, 340-345
139. Yvon, A.M., Wadsworth, P. and Jordan, M.A. (1999) Taxol suppresses dynamics of individual microtubules in living human tumor cells. Mol. Biol. Cell 10, 947-959
140. Lyseng-Williamson, K.A. and Fenton, C. (2005) Docetaxel: a review of its use in metastatic breast cancer. Drugs 65, 2513-2531
141. Sarkar, F.H., Li, Y., Wang, Z., Kong, D. and Ali, S. (2010) Implication of microRNAs in drug resistance for designing novel cancer therapy. Drug Resist. Updat. 13, 57-66
142. Xie, L., Chen, X., Wang, L., Qian, X., Wang, T., Wei, J., Yu, L., Ding, Y., Zhang, C. and Liu, B. (2010) Cell-free miRNAs may indicate diagnosis and docetaxel sensitivity of tumor cells in malignant effusions. BMC Cancer 10, 591
143. Chatterjee, A., Chattopadhyay, D. and Chakrabarti, G. (2014) miR-17-5p downregulation contributes to paclitaxel resistance of lung cancer cells through altering Beclin1 expression. PLoS One 9, e95716
144. Feng, B., Wang, R. and Chen, L.B. (2012) MiR-100 Resensitizes docetaxel-resistant human lung adenocarcinoma cells (SPC-A1) to docetaxel by targeting Plk1. Cancer Lett. 317, 184-191
145. Cui, S.Y., Huang, J.Y., Chen, Y.T., Song, H.Z., Feng, B., Huang, G.C., Wang, R., Chen, L.B. and De, W. (2013) Let-7c governs the acquisition of chemo- or radioresistance and epithelial-to-mesenchymal transition phenotypes in docetaxel-resistant lung adenocarcinoma. Mol. Cancer Res. 11, 699-713
146. Liu, R., Liu, X., Zheng, Y., Gu, J., Xiong, S., Jiang, P., Jiang, X., Huang, E., Yang, Y., Ge, D. et al. (2014) MicroRNA-7 sensitizes non-small cell lung cancer cells to paclitaxel. Oncol. Lett. 8, 2193-2200
147. Pao, W., Miller, V.A., Politi, K.A., Riely, G.J., Somwar, R., Zakowski, M.F., Kris, M.G. and Varmus, H. (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2, e73
148. Engelman, J.A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J.O., Lindeman, N., Gale, C.M., Zhao, X., Christensen, J. et al. (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316, 1039-1043
149. Weiss, G.J., Bemis, L.T., Nakajima, E., Sugita, M., Birks, D.K., Robinson, W.A., Varella-Garcia, M., Bunn, Jr, P.A., Haney, J., Helfrich, B.A. et al. (2008) EGFR regulation by microRNA in lung cancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines. Ann. Oncol. 19, 1053-1059
150. Dacic, S., Kelly, L., Shuai, Y. and Nikiforova, M.N. (2010) miRNA expression profiling of lung adenocarcinomas: correlation with mutational status. Mod. Pathol. 23, 1577-1582
151. Sos, M.L., Koker, M., Weir, B.A., Heynck, S., Rabinovsky, R., Zander, T., Seeger, J.M., Weiss, J., Fischer, F., Frommolt, P. et al. (2009) PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR. Cancer Res. 69, 3256-3261
152. Suda, K., Murakami, I., Katayama, T., Tomizawa, K., Osada, H., Sekido, Y., Maehara, Y., Yatabe, Y. and Mitsudomi, T. (2010) Reciprocal and complementary role of MET amplification and EGFR T790M mutation in acquired resistance to kinase inhibitors in lung cancer. Clin. Cancer Res. 16, 5489-5498
153. Zhou, Y.M., Liu, J. and Sun, W. (2014) MiR-130a overcomes gefitinib resistance by targeting met in non-small cell lung cancer cell lines. Asian Pac. J. Cancer Prev. 15, 1391-1396
154. Rho, J.K., Choi, Y.J., Lee, J.K., Ryoo, B.Y., Na, I.I., Yang, S.H., Kim, C.H. and Lee, J.C. (2009) Epithelial to mesenchymal transition derived from repeated exposure to gefitinib determines the sensitivity to EGFR inhibitors in A549, a non-small cell lung cancer cell line. Lung Cancer 63, 219-226
155. Suda, K., Tomizawa, K., Fujii, M., Murakami, H., Osada, H., Maehara, Y., Yatabe, Y., Sekido, Y. and Mitsudomi, T. (2011) Epithelial to mesenchymal transition in an epidermal growth factor receptor-mutant lung cancer cell line with acquired resistance to erlotinib. J. Thorac. Oncol. 6, 1152-1161
156. Bryant, J.L., Britson, J., Balko, J.M., Willian, M., Timmons, R., Frolov, A. and Black, E.P. (2012) A microRNA gene expression signature predicts response to erlotinib in epithelial cancer cell lines and targets EMT. Br. J. Cancer 106, 148-156
157. Lee, C.G., McCarthy, S., Gruidl, M., Timme, C. and Yeatman, T.J. (2014) MicroRNA-147 induces a mesenchymal-to-epithelial transition (MET) and reverses EGFR inhibitor resistance. PLoS One 9, e84597
158. Zhao, J., Kelnar, K. and Bader, A.G. (2014) In-depth analysis shows synergy between erlotinib and miR-34a. PLoS One 9, e89105
159. Duan, W., Xu, Y., Dong, Y., Cao, L., Tong, J. and Zhou, X. (2013) Ectopic expression of miR-34a enhances radiosensitivity of non-small cell lung cancer cells, partly by suppressing the LyGDI signaling pathway. J. Radiat. Res. 54, 611-619
160. Tanaka, K., Babic, I., Nathanson, D., Akhavan, D., Guo, D., Gini, B., Dang, J., Zhu, S., Yang, H., De Jesus, J. et al. (2011) Oncogenic EGFR signaling activates an mTORC2-NF-kB pathway that promotes chemotherapy resistance. Cancer Discov. 1, 524-538
161. Lee, K.M., Choi, E.J. and Kim, I.A. (2011) microRNA-7 increases radiosensitivity of human cancer cells with activated EGFR-associated signaling. Radiother. Oncol. 101, 171-176
162. Weidhaas, J.B., Babar, I., Nallur, S.M., Trang, P., Roush, S., Boehm, M., Gillespie, E. and Slack, F.J. (2007) MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. Cancer Res. 67, 11111-11116
163. Oh, J.S., Kim, J.J., Byun, J.Y. and Kim, I.A. (2010) Lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-Ras. Int. J. Radiat. Oncol. Biol. Phys. 76, 5-8
164. Salim, H., Akbar, N.S., Zong, D., Vaculova, A.H., Lewensohn, R., Moshfegh, A., Viktorsson, K. and Zhivotovsky, B. (2012) miRNA-214 modulates radiotherapy response of non-small cell lung cancer cells through regulation of p38MAPK, apoptosis and senescence. Br. J. Cancer 107, 1361-1373
165. Meng, F., Henson, R., Lang, M., Wehbe, H., Maheshwari, S., Mendell, J.T., Jiang, J., Schmittgen, T.D. and Patel, T. (2006) Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology 130, 2113-2129
166. Tryndyak, V.P., Beland, F.A. and Pogribny, I.P. (2010) 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 126, 2575-2583
167. Iliopoulos, D., Lindahl-Allen, M., Polytarchou, C., Hirsch, H.A., Tsichlis, P.N. and Struhl, K. (2010) Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells. Mol. Cell 39, 761-772
168. Lanford, R.E., Hildebrandt-Eriksen, E.S., Petri, A., Persson, R., Lindow, M., Munk, M.E., Kauppinen, S. and Ørum, H. (2010) Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327, 198-201
169. Janssen, H.L., Reesink, H.W., Lawitz, E.J., Zeuzem, S., Rodriguez-Torres, M., Patel, K., van der Meer, A.J., Patick, A.K., Chen, A., Zhou, Y. et al. (2013) Treatment of HCV infection by targeting microRNA. N. Engl. J. Med. 368, 1685-1694
170. Bouchie, A. (2013) First microRNA mimic enters clinic. Nat. Biotechnol. 31, 577