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MicroRNA-1280 Inhibits Invasion and Metastasis by Targeting ROCK1 in Bladder Cancer

Authors
 Shahana Majid  ;  Altaf A. Dar  ;  Sharanjot Saini  ;  Varahram Shahryari  ;  Sumit Arora  ;  Mohd Saif Zaman  ;  Inik Chang  ;  Soichiro Yamamura  ;  Takeshi Chiyomaru  ;  Shinichiro Fukuhara  ;  Yuichiro Tanaka  ;  Guoren Deng  ;  Z. Laura Tabatabai  ;  Rajvir Dahiya 
Citation
 PLoS One, Vol.7(10) : e46743, 2012 
Journal Title
 PLoS One 
ISSN
 1932-6203 
Issue Date
2012
Abstract
MicroRNAs (miRNAs) are non-protein-coding sequences that can function as oncogenes or tumor suppressor genes. This study documents the tumor suppressor role of miR-1280 in bladder cancer. Quantitative real-time PCR and in situ hybridization analyses showed that miR-1280 is significantly down-regulated in bladder cancer cell lines and tumors compared to a non-malignant cell line or normal tissue samples. To decipher the functional significance of miR-1280 in bladder cancer, we ectopically over-expressed miR-1280 in bladder cancer cell lines. Over-expression of miR-1280 had antiproliferative effects and impaired colony formation of bladder cancer cell lines. FACS (fluorescence activated cell sorting) analysis revealed that re-expression of miR-1280 in bladder cancer cells induced G2-M cell cycle arrest and apoptosis. Our results demonstrate that miR-1280 inhibited migration and invasion of bladder cancer cell lines. miR-1280 also attenuated ROCK1 and RhoC protein expression. Luciferase reporter assays demonstrated that oncogene ROCK1 is a direct target of miR-1280 in bladder cancer. This study also indicates that miR-1280 may be of diagnostic and prognostic importance in bladder cancer. For instance, ROC analysis showed that miR-1280 expression can distinguish between malignant and normal bladder cancer cases and Kaplan-Meier analysis revealed that patients with miR-1280 high expression had higher overall survival compared to those with low miR-1280 expression. In conclusion, this is the first study to document that miR-1280 functions as a tumor suppressor by targeting oncogene ROCK1 to invasion/migration and metastasis. Various compounds are currently being used as ROCK1 inhibitors; therefore restoration of tumor suppressor miR-1280 might be therapeutically useful either alone or in combination with these compounds in the treatment of bladder cancer.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91744
DOI
10.1371/journal.pone.0046743
Appears in Collections:
1. Journal Papers (연구논문) > 2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실)
Yonsei Authors
장인익(Chang, In Ik)
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