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MicroRNA Gene Expression Deregulation in Human Breast Cancer

¹ Comprehensive Cancer Center, Ohio State University, Columbus, Ohio; ² Dipartimento di Medicina Sperimentale e Diagnostica, e Centro Interdipartimentale per la Ricerca sul Cancro, Università di Ferrara, Ferrara, Italy; ³ Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy; Departments of ⁴ Pathology, Anatomy and Cell Biology and ⁵ Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania; and ⁶ Ce.S.I. Aging Research Center, Chieti, Italy

Requests for reprints: Carlo M. Croce, Comprehensive Cancer Center, Ohio State University, Room 445C, Wiseman Hall, 400 12th Avenue, Columbus, OH 43210. Phone: 614-292-3063; Fax: 614-292-3312; E-mail: Carlo.Croce{at}osumc.edu.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. Indeed, miRNA aberrant expression has been previously found in human chronic lymphocytic leukemias, where miRNA signatures were associated with specific clinicobiological features. Here, we show that, compared with normal breast tissue, miRNAs are also aberrantly expressed in human breast cancer. The overall miRNA expression could clearly separate normal versus cancer tissues, with the most significantly deregulated miRNAs being mir-125b, mir-145, mir-21, and mir-155. Results were confirmed by microarray and Northern blot analyses. We could identify miRNAs whose expression was correlated with specific breast cancer biopathologic features, such as estrogen and progesterone receptor expression, tumor stage, vascular invasion, or proliferation index.

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				A. Hudder and R. F. Novak miRNAs: Effectors of Environmental Influences on Gene Expression and Disease Toxicol. Sci., June 1, 2008; 103(2): 228 - 240. [Abstract] [Full Text] [PDF]

				M. Jongen-Lavrencic, S. M. Sun, M. K. Dijkstra, P. J. M. Valk, and B. Lowenberg MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia Blood, May 15, 2008; 111(10): 5078 - 5085. [Abstract] [Full Text] [PDF]

				M. N. Nikiforova, G. C. Tseng, D. Steward, D. Diorio, and Y. E. Nikiforov MicroRNA Expression Profiling of Thyroid Tumors: Biological Significance and Diagnostic Utility J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1600 - 1608. [Abstract] [Full Text] [PDF]

				J.-W. Lee, C. H. Choi, J.-J. Choi, Y.-A. Park, S.-J. Kim, S. Y. Hwang, W. Y. Kim, T.-J. Kim, J.-H. Lee, B.-G. Kim, et al. Altered MicroRNA Expression in Cervical Carcinomas Clin. Cancer Res., May 1, 2008; 14(9): 2535 - 2542. [Abstract] [Full Text] [PDF]

				E. J. Nam, H. Yoon, S. W. Kim, H. Kim, Y. T. Kim, J. H. Kim, J. W. Kim, and S. Kim MicroRNA Expression Profiles in Serous Ovarian Carcinoma Clin. Cancer Res., May 1, 2008; 14(9): 2690 - 2695. [Abstract] [Full Text] [PDF]

				S. Sengupta, J. A. den Boon, I-H. Chen, M. A. Newton, S. A. Stanhope, Y.-J. Cheng, C.-J. Chen, A. Hildesheim, B. Sugden, and P. Ahlquist MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins PNAS, April 15, 2008; 105(15): 5874 - 5878. [Abstract] [Full Text] [PDF]

				G. A. Calin and C. M. Croce MicroRNA-Cancer Connection: The Beginning of a New Tale Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 667 - 675. [Abstract] [Full Text] [PDF]

				K.-i. Kozaki, I. Imoto, S. Mogi, K. Omura, and J. Inazawa Exploration of Tumor-Suppressive MicroRNAs Silenced by DNA Hypermethylation in Oral Cancer Cancer Res., April 1, 2008; 68(7): 2094 - 2105. [Abstract] [Full Text] [PDF]

				A. Cohen, M. Shmoish, L. Levi, U. Cheruti, B. Levavi-Sivan, and E. Lubzens Alterations in Micro-Ribonucleic Acid Expression Profiles Reveal a Novel Pathway for Estrogen Regulation Endocrinology, April 1, 2008; 149(4): 1687 - 1696. [Abstract] [Full Text] [PDF]

				C. Zhang MicroRNomics: a newly emerging approach for disease biology Physiol Genomics, April 1, 2008; 33(2): 139 - 147. [Abstract] [Full Text] [PDF]

				D. Landi, F. Gemignani, A. Naccarati, B. Pardini, P. Vodicka, L. Vodickova, J. Novotny, A. Forsti, K. Hemminki, F. Canzian, et al. Polymorphisms within micro-RNA-binding sites and risk of sporadic colorectal cancer Carcinogenesis, March 1, 2008; 29(3): 579 - 584. [Abstract] [Full Text] [PDF]

				C. Camps, F. M. Buffa, S. Colella, J. Moore, C. Sotiriou, H. Sheldon, A. L. Harris, J. M. Gleadle, and J. Ragoussis hsa-miR-210 Is Induced by Hypoxia and Is an Independent Prognostic Factor in Breast Cancer Clin. Cancer Res., March 1, 2008; 14(5): 1340 - 1348. [Abstract] [Full Text] [PDF]

				A. Feber, L. Xi, J. D. Luketich, A. Pennathur, R. J. Landreneau, M. Wu, S. J. Swanson, T. E. Godfrey, and V. R. Litle MicroRNA expression profiles of esophageal cancer. J. Thorac. Cardiovasc. Surg., February 1, 2008; 135(2): 255 - 260. [Abstract] [Full Text] [PDF]

				Q. Yin, X. Wang, J. McBride, C. Fewell, and E. Flemington B-cell Receptor Activation Induces BIC/miR-155 Expression through a Conserved AP-1 Element J. Biol. Chem., February 1, 2008; 283(5): 2654 - 2662. [Abstract] [Full Text] [PDF]

				A. J. Schetter, S. Y. Leung, J. J. Sohn, K. A. Zanetti, E. D. Bowman, N. Yanaihara, S. T. Yuen, T. L. Chan, D. L. W. Kwong, G. K. H. Au, et al. MicroRNA Expression Profiles Associated With Prognosis and Therapeutic Outcome in Colon Adenocarcinoma JAMA, January 30, 2008; 299(4): 425 - 436. [Abstract] [Full Text] [PDF]

				H. Yang, W. Kong, L. He, J.-J. Zhao, J. D. O'Donnell, J. Wang, R. M. Wenham, D. Coppola, P. A. Kruk, S. V. Nicosia, et al. MicroRNA Expression Profiling in Human Ovarian Cancer: miR-214 Induces Cell Survival and Cisplatin Resistance by Targeting PTEN Cancer Res., January 15, 2008; 68(2): 425 - 433. [Abstract] [Full Text] [PDF]

				A. J. Lowery, N. Miller, R. E. McNeill, and M. J. Kerin MicroRNAs as Prognostic Indicators and Therapeutic Targets: Potential Effect on Breast Cancer Management Clin. Cancer Res., January 15, 2008; 14(2): 360 - 365. [Abstract] [Full Text] [PDF]

				J. Jiang, Y. Gusev, I. Aderca, T. A. Mettler, D. M. Nagorney, D. J. Brackett, L. R. Roberts, and T. D. Schmittgen Association of MicroRNA Expression in Hepatocellular Carcinomas with Hepatitis Infection, Cirrhosis, and Patient Survival Clin. Cancer Res., January 15, 2008; 14(2): 419 - 427. [Abstract] [Full Text] [PDF]