EIF2C, Dicer, and Drosha are up-regulated along tumor progression and associated with poor prognosis in bladder carcinoma

EIF2C, Dicer, and Drosha are microRNA-regulating machinery components, which participate in microRNA intracellular process and transfer. Our research demonstrated the expression and clinical role of the microRNA-regulating machinery in bladder cancer. EIF2C1, EIF2C2, Dicer, and Drosha mRNA and protein levels were analyzed in 100 bladder carcinomas and 50 normal bladder tissues using quantitative polymerase chain reaction and Western blotting. EIF2C2, Dicer, and Drosha mRNAs and proteins were overexpressed in carcinoma compared with normal tissues, whereas EIF2C1 mRNA and protein were not obviously different. Moreover, immunohistochemistry was used to detect the expressions of EIF2C2, Dicer, and Drosha in 100 bladder carcinomas. There were higher EIF2C2, Dicer, and Drosha expressions in carcinomas than in the adjacent normal tissues, positive correlations being noted with clinical stage, histopathologic grade, and recurrence. Higher EIF2C2, Dicer, and Drosha expressions were related to shorter cancer-specific survival and shorter recurrence-free survival. Multivariate Cox analysis showed that EIF2C2 was an important risk factor in bladder cancer. In conclusion, EIF2C2, Dicer, and Drosha are more highly expressed in bladder carcinoma, promote the development of bladder cancer, and suggested a poor prognosis. Their clinical role in bladder carcinoma merits further research.

[1]  C. Creighton,et al.  A dosage-dependent pleiotropic role of Dicer in prostate cancer growth and metastasis , 2013, Oncogene.

[2]  P. Zhang,et al.  Dicer is down-regulated in clear cell renal cell carcinoma and in vitro Dicer knockdown enhances malignant phenotype transformation. , 2014, Urologic oncology.

[3]  Y. Kitade,et al.  Bioenergetics and Gene Silencing Approaches for Unraveling Nucleotide Recognition by the Human EIF2C2/Ago2 PAZ Domain , 2014, PloS one.

[4]  S. Siddiqi,et al.  Piwis and piwi‐interacting RNAs in the epigenetics of cancer , 2012, Journal of cellular biochemistry.

[5]  Qicai Liu,et al.  Silencing Dicer expression enhances cellular proliferative and invasive capacities in human tongue squamous cell carcinoma. , 2014, Oncology reports.

[6]  Xiaoyi Huang,et al.  Extracellular MicroRNAs in Urologic Malignancies: Chances and Challenges , 2013, International journal of molecular sciences.

[7]  Guojun Zhang,et al.  High expression of polo-like kinase 1 is associated with the metastasis and recurrence in urothelial carcinoma of bladder. , 2013, Urologic oncology.

[8]  C. Balch,et al.  AJCC Cancer Staging Manual. 6th ed , 2002 .

[9]  A. Scarpa,et al.  Pathology and Genetics , 2010 .

[10]  Ze-Guang Han,et al.  Argonaute2 promotes tumor metastasis by way of up‐regulating focal adhesion kinase expression in hepatocellular carcinoma , 2013, Hepatology.

[11]  B. Davidson,et al.  Argonaute, Dicer, and Drosha are up-regulated along tumor progression in serous ovarian carcinoma. , 2012, Human pathology.

[12]  Chang-qing Yang,et al.  Study on the clinical significance of Argonaute2 expression in colonic carcinoma by tissue microarray. , 2013, International journal of clinical and experimental pathology.

[13]  Sanjeev Gupta,et al.  Prognostic Significance of Deregulated Dicer Expression in Breast Cancer , 2013, PloS one.

[14]  Pu Li,et al.  Genetic Variation in DROSHA 3’UTR Regulated by hsa-miR-27b Is Associated with Bladder Cancer Risk , 2013, PloS one.

[15]  V. Kim,et al.  Regulation of microRNA biogenesis , 2014, Nature Reviews Molecular Cell Biology.

[16]  S. Filetti,et al.  Overexpression of genes involved in miRNA biogenesis in medullary thyroid carcinomas with RET mutation , 2014, Endocrine.

[17]  Leonardo G. Trabuco,et al.  Molecular dissection of human Argonaute proteins by DNA shuffling , 2013, Nature Structural &Molecular Biology.

[18]  P. Graves,et al.  Overexpression of human Argonaute2 inhibits cell and tumor growth. , 2013, Biochimica et biophysica acta.

[19]  L. Sobin,et al.  World Health Organization classification of tumors , 2000, Cancer.

[20]  Mallory A. Havens,et al.  Drosha Promotes Splicing of a Pre-microRNA-like Alternative Exon , 2014, PLoS genetics.

[21]  D. Ornstein.  Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs , 2004 .

[22]  C. Cordon-Cardo,et al.  MicroRNA-126 inhibits invasion in bladder cancer via regulation of ADAM9 , 2014, British Journal of Cancer.

[23]  D. Horst,et al.  Overexpression of Dicer predicts poor survival in colorectal cancer. , 2011, European journal of cancer.

[24]  C. M. Eischen,et al.  Inactivation of p53 is insufficient to allow B cells and B-cell lymphomas to survive without Dicer. , 2014, Cancer research.

[25]  G. Calin,et al.  Hypoxia Mediated Downregulation of miRNA Biogenesis Promotes Tumor Progression , 2014, Nature Communications.

[26]  J. Forbes,et al.  The expression of Dicer and Drosha in matched normal tissues, tumours and lymph node metastases in triple negative breast cancer , 2014, BMC Cancer.

[27]  D. Aoki,et al.  Application of MicroRNA in Diagnosis and Treatment of Ovarian Cancer , 2014, BioMed research international.

[28]  Zhiming Cai,et al.  Inducing cell proliferation inhibition and apoptosis via silencing Dicer, Drosha, and Exportin 5 in urothelial carcinoma of the bladder , 2013, Journal of surgical oncology.

[29]  A. Puisieux,et al.  Epithelial-mesenchymal transition transcription factors and miRNAs: "Plastic surgeons" of breast cancer. , 2014, World journal of clinical oncology.

[30]  Xavier Estivill,et al.  Evidence for the biogenesis of more than 1,000 novel human microRNAs , 2014, Genome Biology.

[31]  Mike W. C. Thang,et al.  Global Assessment of Antrodia cinnamomea-Induced MicroRNA Alterations in Hepatocarcinoma Cells , 2013, PloS one.

[32]  Jan-Fang Cheng,et al.  Dicer, Drosha, and outcomes in patients with ovarian cancer. , 2008, The New England journal of medicine.

[33]  C. Compton,et al.  AJCC Cancer Staging Manual , 2002, Springer New York.

[34]  C. Melo,et al.  MicroRNA biogenesis: dicing assay. , 2014, Methods in molecular biology.

[35]  G. Gordillo,et al.  Dicer Knockdown Inhibits Endothelial Cell Tumor Growth via MicroRNA 21a-3p Targeting of Nox-4* , 2014, The Journal of Biological Chemistry.

[36]  O. Slabý,et al.  Urine microRNAs as potential noninvasive biomarkers in urologic cancers. , 2014, Urologic oncology.

[37]  D. Barford,et al.  Argonaute: A scaffold for the function of short regulatory RNAs. , 2006, Trends in biochemical sciences.

[38]  E. Messing,et al.  Screening for bladder cancer: rationale, limitations, whom to target, and perspectives. , 2013, European urology.

[39]  Ji Xu,et al.  Argonaute 2 promotes myeloma angiogenesis via microRNA dysregulation , 2014, Journal of Hematology & Oncology.

[40]  V. Margulis,et al.  The Role of Systemic Chemotherapy in Management of Upper Tract Urothelial Cancer , 2013, Current Urology Reports.

[41]  Junhua Zheng,et al.  Argonaute 2 is up-regulated in tissues of urothelial carcinoma of bladder. , 2014, International journal of clinical and experimental pathology.

[42]  H. Nakayama,et al.  A low Dicer expression is associated with resistance to 5-FU-based chemoradiotherapy and a shorter overall survival in patients with oral squamous cell carcinoma. , 2014, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[43]  Yilin Yang,et al.  From small to big: microRNAs as new players in medulloblastomas , 2013, Tumor Biology.

[44]  T. Reh,et al.  Conserved microRNA pathway regulates developmental timing of retinal neurogenesis , 2013, Proceedings of the National Academy of Sciences.

[45]  I. Sesterhenn,et al.  World health organization classifications of tumours. pathology and genetics of tumours of the urinary system and male genital organs , 2005 .

[46]  Xiangshan Fan,et al.  Up-regulation of Ago2 expression in gastric carcinoma , 2013, Medical Oncology.

[47]  Xianwei Wang,et al.  Predictive factors for the sensitivity of radiotherapy and prognosis of esophageal squamous cell carcinoma , 2014, International journal of radiation biology.

[48]  Junhua Zheng,et al.  Evaluation of Argonaute protein as a predictive marker for human clear cell renal cell carcinoma. , 2013, International journal of clinical and experimental pathology.

[49]  L. Pfeffer,et al.  Comprehensive Analysis of MicroRNA (miRNA) Targets in Breast Cancer Cells* , 2013, The Journal of Biological Chemistry.