Expression of microRNAs in the urine of patients with bladder cancer.

UNLABELLED We quantified the urine sediment and supernatant levels of microRNA (miRNA) targets related to epithelial-mesenchymal transition in 51 patients with bladder cancer and in 24 controls. We found that patients with bladder cancer had depressed levels of the miR-200 family, miR-192, and miR-155 in urinary sediment. The urinary level of these miRNAs may be developed as noninvasive markers for bladder cancer. BACKGROUND MicroRNAs (miRNA) have been implicated to play an important role in the pathogenesis of a variety of cancers. We studied the levels of miRNAs related to epithelial-mesenchymal transition (EMT) in the urine of patients with bladder cancer. METHOD The expression of the miR-200 family, miR-205, miR-192, miR-155, and miR-146a in the urine sediment and supernatant of 51 patients with bladder cancer and in 24 controls was determined by real-time quantitative polymerase chain reaction. RESULTS Compared with controls, the patients with bladder cancer had a lower expression of the miR-200 family, miR-192, and miR-155 in the urinary sediment; lower expression of miR-192; and higher expression of miR-155 in the urinary supernatant. The expression of the miR-200 family, miR-205, and miR-192 in the urine sediment significantly correlated with urinary expression of EMT markers, including zinc finger E-box-binding homeobox 1, vimentin, transforming growth factor β1, and Ras homolog gene family, member A. Furthermore, the levels of miR-200c and miR-141 in the urine sediment became normalized after surgery. CONCLUSION We found that the urinary miR-200 family, miR-155, miR-192, and miR-205 levels are depressed in patients with bladder cancer. The level of these miRNA targets in urine has the potential to be developed as noninvasive markers for bladder cancer.

[1]  Dieter Jocham,et al.  A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. , 2010, Urologic oncology.

[2]  Gang Wang,et al.  Serum and Urinary Cell–free MiR-146a and MiR-155 in Patients with Systemic Lupus Erythematosus , 2010, The Journal of Rheumatology.

[3]  A. Jemal,et al.  Cancer Statistics, 2009 , 2009, CA: a cancer journal for clinicians.

[4]  Lianbo Yu,et al.  Detection of microRNA Expression in Human Peripheral Blood Microvesicles , 2008, PloS one.

[5]  John J Rossi,et al.  MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-β-induced collagen expression via inhibition of E-box repressors , 2007, Proceedings of the National Academy of Sciences.

[6]  Yariv Yogev,et al.  Serum MicroRNAs Are Promising Novel Biomarkers , 2008, PloS one.

[7]  Jørgen Kjems,et al.  Coordinated epigenetic repression of the miR‐200 family and miR‐205 in invasive bladder cancer , 2011, International journal of cancer.

[8]  E. Li,et al.  Serum and urinary free microRNA level in patients with systemic lupus erythematosus , 2011, Lupus.

[9]  K. Rieger-Christ,et al.  A MicroRNA expression profile defining the invasive bladder tumor phenotype. , 2011, Urologic oncology.

[10]  R. Plasterk,et al.  The diverse functions of microRNAs in animal development and disease. , 2006, Developmental cell.

[11]  Domenico Coppola,et al.  MicroRNA-155 Is Regulated by the Transforming Growth Factor β/Smad Pathway and Contributes to Epithelial Cell Plasticity by Targeting RhoA , 2008, Molecular and Cellular Biology.

[12]  Woonyoung Choi,et al.  miR-200 Expression Regulates Epithelial-to-Mesenchymal Transition in Bladder Cancer Cells and Reverses Resistance to Epidermal Growth Factor Receptor Therapy , 2009, Clinical Cancer Research.

[13]  E. Miska,et al.  MicroRNA functions in animal development and human disease , 2005, Development.

[14]  A. Hamilton MicroRNA in erythrocytes. , 2010, Biochemical Society transactions.

[15]  V. Zoumpourlis,et al.  Environmental factors and genetic susceptibility promote urinary bladder cancer. , 2010, Toxicology letters.

[16]  Tianhua Zhou,et al.  Down-regulation of miR-141 in gastric cancer and its involvement in cell growth , 2009, Journal of Gastroenterology.

[17]  Michael K. Wendt,et al.  Mechanisms of the epithelial-mesenchymal transition by TGF-beta. , 2009, Future oncology.

[18]  G. Tsujimoto,et al.  Identification of novel microRNA targets based on microRNA signatures in bladder cancer , 2009, International journal of cancer.

[19]  D. Farber,et al.  Transfer of MicroRNAs by Embryonic Stem Cell Microvesicles , 2009, PloS one.

[20]  R. Millikan,et al.  Correlation of metastasis related gene expression and relapse-free survival in patients with locally advanced bladder cancer treated with cystectomy and chemotherapy. , 2004, The Journal of urology.

[21]  Gang Wang,et al.  Expression of MicroRNAs in the Urinary Sediment of Patients with IgA Nephropathy , 2010, Disease markers.

[22]  Gang Wang,et al.  Expression of miR-146a and miR-155 in the urinary sediment of systemic lupus erythematosus , 2012, Clinical Rheumatology.

[23]  Å. Borg,et al.  MiRNA expression in urothelial carcinomas: Important roles of miR‐10a, miR‐222, miR‐125b, miR‐7 and miR‐452 for tumor stage and metastasis, and frequent homozygous losses of miR‐31 , 2009, International journal of cancer.

[24]  Alexander Pertsemlidis,et al.  Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. , 2009, Genes & development.

[25]  Hideo Baba,et al.  Epithelial–mesenchymal transition in cancer development and its clinical significance , 2010, Cancer science.

[26]  Sun-Mi Park,et al.  The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. , 2008, Genes & development.