Identification of the miR-106b∼25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation

Science Signaling

Volumn 3, Issue 117, 2010, Pages

  Poliseno, Laura ^a   Salmena, Leonardo ^a   Riccardi, Luisa ^a   Fornari, Alessandro ^b,c   Song, Min Sup ^a   Hobbs, Robin M ^a   Sportoletti, Paolo ^a   Varmeh, Shorheh ^a   Egia, Ainara ^a   Fedele, Giuseppe ^b,d   Rameh, Lucia ^e   Loda, Massimo ^b,d   Pandolfi, Pier Paolo ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b DANA FARBER CANCER INSTITUTE   (United States)

^c UNIVERSITY OF TURIN   (Italy)

^d BRIGHAM AND WOMEN S HOSPITAL   (United States)

^e BOSTON BIOMEDICAL RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DICER; MICRORNA; MICRORNA 22; MICRORNA 25; MICRORNA 302; MINICHROMOSOME MAINTENANCE PROTEIN 7; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CARCINOGENESIS; CELL TRANSFORMATION; CONTROLLED STUDY; EMBRYO; GENE CLUSTER; GENE IDENTIFICATION; GENE LOCUS; GENE OVEREXPRESSION; GENE TARGETING; GENETIC TRANSFORMATION; HOST; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INTRON; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; PROSTATIC INTRAEPITHELIAL NEOPLASIA; PROTO ONCOGENE; REGULATORY MECHANISM; RNA PROCESSING; TRANSGENIC MOUSE;

ANIMALS; CELL CYCLE PROTEINS; CELL TRANSFORMATION, NEOPLASTIC; DNA-BINDING PROTEINS; HUMANS; INTRONS; MALE; MICE; MICE, TRANSGENIC; MICRORNAS; MULTIGENE FAMILY; NUCLEAR PROTEINS; PROSTATIC NEOPLASMS; PROTO-ONCOGENES; PTEN PHOSPHOHYDROLASE;

MUS MUSCULUS;

EID: 77953948708     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.2000594     Document Type: Article

References (56)

1. Nomenclature: PTEN, human protein; PTEN, human mRNA and gene; Pten, mouse protein; Pten, mouse mRNA and gene; DICER, human protein; DICER, human mRNA or gene; MCM7, human protein; MCM7, human mRNA and gene; miR-X, mature miRNA; miR-X, miRNA gene.
2. V. N. Kim, J. Han, M. C. Siomi, Biogenesis of small RNAs in animals. Nat. Rev. Mol. Cell Biol. 10, 126-139 (2009).
3. M. S. Kumar, J. Lu, K. L. Mercer, T. R. Golub, T. Jacks, Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat. Genet. 39, 673-677 (2007).
4. S. Chiosea, E. Jelezcova, U. Chandran, M. Acquafondata, T. McHale, R. W. Sobol, R. Dhir, Up-regulation of Dicer, a component of the microRNA machinery, in prostate adenocarcinoma. Am. J. Pathol. 169, 1812-1820 (2006).
5. S. Baskerville, D. P. Bartel, Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 11, 241-247 (2005).
6. E. van Rooij, L. B. Sutherland, X. Qi, J. A. Richardson, J. Hill, E. N. Olson, Control of stressdependent cardiac growth and gene expression by a microRNA. Science 316, 575-579 (2007).
7. A. Grimson, K. K. Farh, W. K. Johnston, P. Garrett-Engele, L. P. Lim, D. P. Bartel, MicroRNA targeting specificity in mammals: Determinants beyond seed pairing. Mol. Cell 27, 91-105 (2007).
8. W. Filipowicz, S. N. Bhattacharyya, N. Sonenberg, Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight? Nat. Rev. Genet. 9, 102-114 (2008).
9. P. Landgraf, M. Rusu, R. Sheridan, A. Sewer, N. Iovino, A. Aravin, S. Pfeffer, A. Rice, A. O. Kamphorst, M. Landthaler, C. Lin, N. D. Socci, L. Hermida, V. Fulci, S. Chiaretti, R. Foá, J. Schliwka, U. Fuchs, A. Novosel, R. U. Muller, B. Schermer, U. Bissels, J. Inman, Q. Phan, M. Chien, D. B. Weir, R. Choksi, G. De Vita, D. Frezzetti, H. I. Trompeter, V. Hornung, G. Teng, G. Hartmann, M. Palkovits, R. Di Lauro, P. Wernet, G. Macino, C. E. Rogler, J. W. Nagle, J. Ju, F. N. Papavasiliou, T. Benzing, P. Lichter, W. Tam, M. J. Brownstein, A. Bosio, A. Borkhardt, J. J. Russo, C. Sander, M. Zavolan, T. Tuschl, A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129, 1401-1414 (2007).
10. A. Ventura, T. Jacks, MicroRNAs and cancer: Short RNAs go a long way. Cell 136, 586-591 (2009).
11. B. D. Manning, L. C. Cantley, AKT/PKB signaling: Navigating downstream. Cell 129, 1261-1274 (2007).
12. L. Salmena, A. Carracedo, P. P. Pandolfi, Tenets of PTEN tumor suppression. Cell 133, 403-414 (2008).
13. L. C. Trotman, M. Niki, Z. A. Dotan, J. A. Koutcher, A. Di Cristofano, A. Xiao, A. S. Khoo, P. Roy-Burman, N. M. Greenberg, T. Van Dyke, C. Cordon-Cardo, P. P. Pandolfi, Pten dose dictates cancer progression in the prostate. sPLoS Biol. 1, E59 (2003).
14. B. P. Lewis, C. B. Burge, D. P. Bartel, Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20 (2005).
15. A. Krek, D. Grun, M. N. Poy, R. Wolf, L. Rosenberg, E. J. Epstein, P. MacMenamin, I. da Piedade, K. C. Gunsalus, M. Stoffel, N. Rajewsky, Combinatorial microRNA target predictions. Nat. Genet. 37, 495-500 (2005).
16. B. John, A. J. Enright, A. Aravin, T. Tuschl, C. Sander, D. S. Marks, Human microRNA targets. PLoS Biol. 2, e363 (2004).
17. S. Griffiths-Jones, R. J. Grocock, S. van Dongen, A. Bateman, A. J. Enright, miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 34, D140-D144 (2006).
18. S. B. Koralov, S. A. Muljo, G. R. Galler, A. Krek, T. Chakraborty, C. Kanellopoulou, K. Jensen, B. S. Cobb, M. Merkenschlager, N. Rajewsky, K. Rajewsky, Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell 132, 860-874 (2008).
19. C. Xiao, L. Srinivasan, D. P. Calado, H. C. Patterson, B. Zhang, J. Wang, J. M. Henderson, J. L. Kutok, K. Rajewsky, Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat. Immunol. 9, 405-414 (2008).
20. B. P. Lewis, I. H. Shih, M. W. Jones-Rhoades, D. P. Bartel, C. B. Burge, Prediction of mammalian microRNA targets. Cell 115, 787-798 (2003).
21. S. Takakura, N. Mitsutake, M. Nakashima, H. Namba, V. A. Saenko, T. I. Rogounovitch, Y. Nakazawa, T. Hayashi, A. Ohtsuru, S. Yamashita, Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells. Cancer Sci. 99, 1147-1154 (2008).
22. M. P. Myers, J. P. Stolarov, C. Eng, J. Li, S. I. Wang, M. H. Wigler, R. Parsons, N. K. Tonks, P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase. Proc. Natl. Acad. Sci. U. S. A. 94, 9052-9057 (1997).
23. J. G. Doench, P. A. Sharp, Specificity of microRNA target selection in translational repression. Genes Dev. 18, 504-511 (2004).
24. P. M. Voorhoeve, C. le Sage, M. Schrier, A. J. Gillis, H. Stoop, R. Nagel, Y. P. Liu, J. van Duijse, J. Drost, A. Griekspoor, E. Zlotorynski, N. Yabuta, G. De Vita, H. Nojima, L. H. Looijenga, R. Agami, A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell 124, 1169-1181 (2006).
25. S. Ambs, R. L. Prueitt, M. Yi, R. S. Hudson, T. M. Howe, F. Petrocca, T. A. Wallace, C. G. Liu, S. Volinia, G. A. Calin, H. G. Yfantis, R. M. Stephens, C. M. Croce, Genomic profiling of microRNA and messenger RNA reveals deregulated microRNA expression in prostate cancer. Cancer Res. 68, 6162-6170 (2008).
26. S. Volinia, G. A. Calin, C. G. Liu, S. Ambs, A. Cimmino, F. Petrocca, R. Visone, M. Iorio, C. Roldo, M. Ferracin, R. L. Prueitt, N. Yanaihara, G. Lanza, A. Scarpa, A. Vecchione, M. Negrini, C. C. Harris, C. M. Croce, A microRNA expression signature of human solid tumors defines cancer gene targets. Proc. Natl. Acad. Sci. U. S. A. 103, 2257-2261 (2006).
27. C. D. Scharer, C. D. McCabe, M. Ali-Seyed, M. F. Berger, M. L. Bulyk, C. S. Moreno, Genome-wide promoter analysis of the SOX4 transcriptional network in prostate cancer cells. Cancer Res. 69, 709-717 (2009).
28. A. Costa, S. Onesti, The MCM complex: (Just) a replicative helicase? Biochem. Soc. Trans. 36, 136-140 (2008).
29. M. H. Levesque, M. El-Alfy, L. Berger, F. Labrie, C. Labrie, Evaluation of AIbZIP and Cdc47 as markers for human prostatic diseases. Urology 69, 196-201 (2007).
30. S. McCarthy, A. Caporali, S. Enkemann, M. Scaltriti, S. Eschrich, P. Davalli, A. Corti, A. Lee, J. Sung, T. J. Yeatman, S. Bettuzzi, Green tea catechins suppress the DNA synthesis marker MCM7 in the TRAMP model of prostate cancer. Mol. Oncol. 1, 196-204 (2007).
31. S. Laitinen, P. M. Martikainen, T. Tolonen, J. Isola, T. L. Tammela, T. Visakorpi, EZH2, Ki-67 and MCM7 are prognostic markers in prostatectomy treated patients. Int. J. Cancer 122, 595-602 (2008).
32. Z. Chen, L. C. Trotman, D. Shaffer, H. K. Lin, Z. A. Dotan, M. Niki, J. A. Koutcher, H. I. Scher, T. Ludwig, W. Gerald, C. Cordon-Cardo, P. P. Pandolfi, Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436, 725-730 (2005).
33. C. Nardella, Z. Chen, L. Salmena, A. Carracedo, A. Alimonti, A. Egia, B. Carver, W. Gerald, C. Cordon-Cardo, P. P. Pandolfi, Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are cooperative oncogenic events. Genes Dev. 22, 2172-2177 (2008).
34. K. Ellwood-Yen, T. G. Graeber, J. Wongvipat, M. L. Iruela-Arispe, J. Zhang, R. Matusik, G. V. Thomas, C. L. Sawyers, Myc-driven murine prostate cancer shares molecular features with human prostate tumors. Cancer Cell 4, 223-238 (2003).
35. Y. Nagata, K. H. Lan, X. Zhou, M. Tan, F. J. Esteva, A. A. Sahin, K. S. Klos, P. Li, B. P. Monia, N. T. Nguyen, G. N. Hortobagyi, M. C. Hung, D. Yu, PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 6, 117-127 (2004).
36. P. K. Majumder, J. J. Yeh, D. J. George, P. G. Febbo, J. Kum, Q. Xue, R. Bikoff, H. Ma, P. W. Kantoff, T. R. Golub, M. Loda, W. R. Sellers, Prostate intraepithelial neoplasia induced by prostate restricted Akt activation: The MPAKT model. Proc. Natl. Acad. Sci. U. S. A. 100, 7841-7846 (2003).
37. B. Ren, G. Yu, G. C. Tseng, K. Cieply, T. Gavel, J. Nelson, G. Michalopoulos, Y. P. Yu, J. H. Luo, MCM7 amplification and overexpression are associated with prostate cancer progression. Oncogene 25, 1090-1098 (2006).
38. Q. Huang, K. Gumireddy, M. Schrier, C. le Sage, R. Nagel, S. Nair, D. A. Egan, A. Li, G. Huang, A. J. Klein-Szanto, P. A. Gimotty, D. Katsaros, G. Coukos, L. Zhang, E. Puré, R. Agami, The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat. Cell Biol. 10, 202-210 (2008).
39. A. M. DeMarzo, W. G. Nelson, W. B. Isaacs, J. I. Epstein, Pathological and molecular aspects of prostate cancer. Lancet 361, 955-964 (2003).
40. B. Gurel, T. Iwata, C. M. Koh, R. B. Jenkins, F. Lan, C. Van Dang, J. L. Hicks, J. Morgan, T. C. Cornish, S. Sutcliffe, W. B. Isaacs, J. Luo, A. M. De Marzo, Nuclear MYC protein overexpression is an early alteration in human prostate carcinogenesis. Mod. Pathol. 21, 1156-1167 (2008).
41. J. H. Schulte, S. Horn, T. Otto, B. Samans, L. C. Heukamp, U. C. Eilers, M. Krause, K. Astrahantseff, L. Klein-Hitpass, R. Buettner, A. Schramm, H. Christiansen, M. Eilers, A. Eggert, B. Berwanger, MYCN regulates oncogenic MicroRNAs in neuroblastoma. Int. J. Cancer 122, 699-704 (2008).
42. J. M. Shohet, M. J. Hicks, S. E. Plon, S. M. Burlingame, S. Stuart, S. Y. Chen, M. K. Brenner, J. G. Nuchtern, Minichromosome maintenance protein MCM7 is a direct target of the MYCN transcription factor in neuroblastoma. Cancer Res. 62, 1123-1128 (2002).
43. A. Koppen, R. Ait-Aissa, J. Koster, P. G. van Sluis, I. Ora, H. N. Caron, R. Volckmann, R. Versteeg, L. J. Valentijn, Direct regulation of the minichromosome maintenance complex by MYCN in neuroblastoma. Eur. J. Cancer 343, 2413-2422 (2007).
44. P. C. Fernandez, S. R. Frank, L. Wang, M. Schroeder, S. Liu, J. Greene, A. Cocito, B. Amati, Genomic targets of the human c-Myc protein. Genes Dev. 17, 1115-1129 (2003).
45. K. A. O'Donnell, E. A. Wentzel, K. I. Zeller, C. V. Dang, J. T. Mendell, c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435, 839-843 (2005).
46. Y. K. Kim, V. N. Kim, Processing of intronic microRNAs. EMBO J. 26, 775-783 (2007).
47. KIP1 cooperate in prostate cancer tumor suppression in the mouse. Nat. Genet. 27, 222-224 (2001).
48. K. A. Honeycutt, Z. Chen, M. I. Koster, M. Miers, J. Nuchtern, J. Hicks, D. R. Roop, J. M. Shohet, Deregulated minichromosomal maintenance protein MCM7 contributes to oncogene driven tumorigenesis. Oncogene 25, 4027-4032 (2006).
49. V. Padmanabhan, P. Callas, G. Philips, T. D. Trainer, B. G. Beatty, DNA replication regulation protein Mcm7 as a marker of proliferation in prostate cancer. J. Clin. Pathol. 57, 1057-1062 (2004).
50. S. Costinean, N. Zanesi, Y. Pekarsky, E. Tili, S. Volinia, N. Heerema, C. M. Croce, Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in Em-miR155 transgenic mice. Proc. Natl. Acad. Sci. U. S. A. 103, 7024-7029 (2006).
51. T. Maeda, R. M. Hobbs, T. Merghoub, I. Guernah, A. Zelent, C. Cordon-Cardo, J. Teruya-Feldstein, P. P. Pandolfi, Role of the proto-oncogene Pokemon in cellular transformation and ARF repression. Nature 433, 278-285 (2005).
52. L. A. Serunian, K. R. Auger, L. C. Cantley, Identification and quantification of polyphosphoinositides produced in response to platelet-derived growth factor stimulation. Methods Enzymol. 198, 78-87 (1991).
53. H. A. Drabkin, C. Parsy, K. Ferguson, F. Guilhot, L. Lacotte, L. Roy, C. Zeng, A. Baron, S. P. Hunger, M. Varella-Garcia, R. Gemmill, F. Brizard, A. Brizard, J. Roche, Quantitative HOX expression in chromosomally defined subsets of acute myelogenous leukemia. Leukemia 16, 186-195 (2002).
54. A. Ventura, A. G. Young, M. M. Winslow, L. Lintault, A. Meissner, S. J. Erkeland, J. Newman, R. T. Bronson, D. Crowley, J. R. Stone, R. Jaenisch, P. A. Sharp, T. Jacks, Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 132, 875-886 (2008).
55. N. R. Smalheiser, V. I. Torvik, Alu elements within human mRNAs are probable microRNA targets. Trends Genet. 22, 532-536 (2006).
56. Acknowledgments: We thank C. Gewinner for providing sh-Ren and sh-PTEN retroviral vectors and for assistance with lipid extraction and growth in semisolid medium; A. Tuccoli for advice in the analysis of the target prediction algorithms; and A. Papa for helpful discussion. Funding: L. P. is supported by a fellowship from the American Italian Cancer Foundation. L. S. is supported by a fellowship from the Canadian Institute of Health Sciences. P. S. is supported in part by the Associazione Umbra Leucemie e Linfomi AULL. P. P. P. is supported by NIH grant R01 CA-82328-0. Author contributions: L. P. and P. P. P. designed the project. L. P., L. S., L. R., A. F., M. S. S., R. M. H., P. S., S. V., A. E., G. F., and L. Ra. performed the experiments. L. P., L. S., L. R., R. M. H., and P. P. P. wrote the paper. M. L., and. supervised the project. All authors critically discussed the results and the manuscript. Competing interests: The authors declare that they do not have any competing financial, personal, or professional interest.