MicroRNA-449a acts as a tumor suppressor in human bladder cancer through the regulation of pocket proteins

Frequent downregulation of microRNA-449a (miR-449a) was detected in 14 human bladder cancer tissues. The restoration of miR-449a inhibited cell growth and induced G1-phase arrest in T24 and 5637 human bladder cancer cells. CDK6 and CDC25a were downregulated after miR-449a treatment, resulting in the...

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Veröffentlicht in:	Cancer letters 2012-07, Vol.320 (1), p.40-47
Hauptverfasser:	Chen, Hong, Lin, Yi-Wei, Mao, Ye-Qing, Wu, Jian, Liu, Yun-Fu, Zheng, Xiang-Yi, Xie, Li-Ping
Format:	Artikel
Sprache:	eng
Schlagworte:	Aged Aged, 80 and over Animals antigens Base Sequence Bladder cancer Cancer Cancer therapies cdc25 Phosphatases - antagonists & inhibitors Cell culture Cell cycle Cell growth Cell Growth Processes - genetics Cell Line, Tumor Crk-Associated Substrate Protein - genetics Crk-Associated Substrate Protein - metabolism Cyclin-Dependent Kinase 6 - antagonists & inhibitors Down-Regulation Female G1 Phase Cell Cycle Checkpoints - genetics Gene Expression Regulation, Neoplastic Grants Hematology, Oncology and Palliative Medicine Humans Kinases Male Mice Mice, Inbred BALB C MicroRNAs MicroRNAs - administration & dosage MicroRNAs - biosynthesis MicroRNAs - genetics Middle Aged miR-449a miRNA Mitochondrial Proteins Molecular Sequence Data Phosphorylation Pocket protein proteins Retinoblastoma protein Retinoblastoma Protein - genetics Retinoblastoma Protein - metabolism Rodents Targeted therapy Transplantation, Heterologous Tumor suppressor genes Tumors Urinary bladder urinary bladder neoplasms Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - metabolism Urinary Bladder Neoplasms - pathology Xenografts
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Zusammenfassung:	Frequent downregulation of microRNA-449a (miR-449a) was detected in 14 human bladder cancer tissues. The restoration of miR-449a inhibited cell growth and induced G1-phase arrest in T24 and 5637 human bladder cancer cells. CDK6 and CDC25a were downregulated after miR-449a treatment, resulting in the functional accumulation of the pocket proteins Rb and p130. The growth of T24 tumor xenografts was suppressed by exogenous miR-449a, and the nuclear proliferation antigen Ki-67 was downregulated in miR-449a-treated tumors. These results suggest a tumor-suppressive role for miR-449a in human bladder cancer.
ISSN:	0304-3835 1872-7980
DOI:	10.1016/j.canlet.2012.01.027