Micro-RNA profiling in kidney and bladder cancers.

OBJECTIVES Micro-RNAs are a group of small noncoding RNAs with modulator activity of gene expression. Recently, micro-RNA genes were found abnormally expressed in several types of cancers. To study the role of the micro-RNAs in human kidney and bladder cancer, we analyzed the expression profile of 245 micro-RNAs in kidney and bladder primary tumors. METHODS AND MATERIALS A total of 27 kidney specimens (20 carcinomas, 4 benign renal tumors, and 3 normal parenchyma) and 27 bladder specimens (25 urothelial carcinomas and 2 normal mucosa) were included in the study. Total RNA was used for hybridization on an oligonucleotide microchip for micro-RNA profiling developed in our laboratories. This microchip contains 368 probes in triplicate, corresponding to 245 human and mouse micro-RNA genes. RESULTS A set of 4 human micro-RNAs (miR-28, miR-185, miR-27, and let-7f-2) were found significantly up-regulated in renal cell carcinoma (P < 0.05) compared to normal kidney. Human micro-RNAs miR-223, miR-26b, miR-221, miR-103-1, miR-185, miR-23b, miR-203, miR-17-5p, miR-23a, and miR-205 were significantly up-regulated in bladder cancers (P < 0.05) compared to normal bladder mucosa. Of the kidney cancers studied, there was no differential micro-RNA expression across various stages, whereas with increasing tumor-nodes-metastasis staging in bladder cancer, miR-26b showed a moderate decreasing trend (P = 0.082). CONCLUSIONS Our results show that different micro-RNAs are deregulated in kidney and bladder cancer, suggesting the involvement of these genes in the development and progression of these malignancies. Further studies are needed to clarify the role of micro-RNAs in neoplastic transformation and to test the potential clinical usefulness of micro-RNAs microarrays as diagnostic and prognostic tool.

[1]  C. Croce,et al.  MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Tara L. Naylor,et al.  microRNAs exhibit high frequency genomic alterations in human cancer. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[3]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[4]  H. Horvitz,et al.  MicroRNA expression profiles classify human cancers , 2005, Nature.

[5]  A. Jemal,et al.  Cancer Statistics, 2006 , 2006, CA: a cancer journal for clinicians.

[6]  M. Crossley,et al.  Eos and Pegasus, Two Members of the Ikaros Family of Proteins with Distinct DNA Binding Activities* , 2000, The Journal of Biological Chemistry.

[7]  G. KOVACS,et al.  Molecular differential pathology of renal cell tumours , 1993, Histopathology.

[8]  Tushar Patel,et al.  Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. , 2006, Gastroenterology.

[9]  S. Hammond MicroRNA therapeutics: a new niche for antisense nucleic acids. , 2006, Trends in molecular medicine.

[10]  C. Croce,et al.  miRNAs, Cancer, and Stem Cell Division , 2005, Cell.

[11]  C. Croce,et al.  MicroRNA-cancer connection: the beginning of a new tale. , 2006, Cancer research.

[12]  Y. Yatabe,et al.  Reduced Expression of the let-7 MicroRNAs in Human Lung Cancers in Association with Shortened Postoperative Survival , 2004, Cancer Research.

[13]  H. Moch,et al.  Chromosomal imbalances are associated with a high risk of progression in early invasive (pT1) urinary bladder cancer. , 1999, Cancer research.

[14]  C. Croce,et al.  MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Y. Yatabe,et al.  A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. , 2005, Cancer research.

[16]  F. Slack,et al.  RAS Is Regulated by the let-7 MicroRNA Family , 2005, Cell.

[17]  Milena B. Furtado,et al.  Homeodomain factor Nkx2-5 in heart development and disease. , 2002, Cold Spring Harbor symposia on quantitative biology.

[18]  S. Lowe,et al.  A microRNA polycistron as a potential human oncogene , 2005, Nature.

[19]  Kathryn A. O’Donnell,et al.  c-Myc-regulated microRNAs modulate E2F1 expression , 2005, Nature.

[20]  G. Maira,et al.  Extensive modulation of a set of microRNAs in primary glioblastoma. , 2005, Biochemical and biophysical research communications.

[21]  R. Baffa,et al.  Molecular genetics of bladder cancer: targets for diagnosis and therapy. , 2006, Journal of experimental & clinical cancer research : CR.

[22]  C. Croce,et al.  Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[23]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[24]  C. Croce,et al.  An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[25]  C. Croce,et al.  MicroRNA gene expression deregulation in human breast cancer. , 2005, Cancer research.

[26]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[27]  R. Stephens,et al.  Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. , 2006, Cancer cell.

[28]  C. Croce,et al.  The role of microRNA genes in papillary thyroid carcinoma. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Muller Fabbri,et al.  A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. , 2005, The New England journal of medicine.