CFTR suppresses tumor progression through miR-193b targeting urokinase plasminogen activator (uPA) in prostate cancer
| Autor: | Kin-Mang Lau, M. Y. Zhao, Chen Xie, J. H. Guo, Wen Guo Jiang, M. K. Yu, Xiaohua Jiang, Xiao Hu Zhang, Ting Ting Sun, Lai Ling Tsang, Chi-Fai Ng, R. Y. Diao, J. D. Dong, Lin Ye, Kin Lam Fok, Z. M. Cai, Jingwan Zhang, Andrew James Sanders, Hsiao Chang Chan, Yiu Wa Chung, Hui Y. Lan, Yifei Wang, Z. J. Xiao |
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| Rok vydání: | 2012 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities Cancer Research medicine.medical_specialty Molecular Sequence Data Cystic Fibrosis Transmembrane Conductance Regulator Down-Regulation Mice Nude Biology Molecular oncology Receptors Urokinase Plasminogen Activator Mice Prostate cancer Growth factor receptor Cell Movement Cell Line Tumor Internal medicine Genetics medicine Animals Humans Molecular Biology Base Sequence Cell growth Prostatic Neoplasms Cancer respiratory system Cell cycle medicine.disease Urokinase-Type Plasminogen Activator Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic Urokinase receptor MicroRNAs Endocrinology Tumor progression Gene Knockdown Techniques Cancer research Female |
| Zdroj: | Oncogene. 32:2282-2291 |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is expressed in the epithelial cells of a wide range of organs/tissues from which most cancers are derived. Although accumulating reports have indicated the association of cancer incidence with genetic variations in CFTR gene, the exact role of CFTR in cancer development and the possible underlying mechanism have not been elucidated. Here, we report that CFTR expression is significantly decreased in both prostate cancer cell lines and human prostate cancer tissue samples. Overexpression of CFTR in prostate cancer cell lines suppresses tumor progression (cell growth, adhesion and migration), whereas knockdown of CFTR leads to enhanced malignancies both in vitro and in vivo. In addition, we demonstrate that CFTR knockdown-enhanced cell proliferation, cell invasion and migration are significantly reversed by antibodies against either urokinase plasminogen activator (uPA) or uPA receptor (uPAR), which are known to be involved in various malignant traits of cancer development. More interestingly, overexpression of CFTR suppresses uPA by upregulating the recently described tumor suppressor microRNA-193b (miR-193b), and overexpression of pre-miR-193b significantly reverses CFTR knockdown-enhanced malignant phenotype and abrogates elevated uPA activity in prostate cancer cell line. Finally, we show that CFTR gene transfer results in significant tumor repression in prostate cancer xenografts in vivo. Taken together, the present study has demonstrated a previously undefined tumor-suppressing role of CFTR and its involvement in regulation of miR-193b in prostate cancer development. |
| Databáze: | OpenAIRE |
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