MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer.
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.
Department of Urology, VA Medical Center and UCSF, San Francisco, California, United States of America.
Shahana
S
Majid
Altaf A
AA
Dar
Sharanjot
S
Saini
Varahram
V
Shahryari
Sumit
S
Arora
Mohd Saif
MS
Zaman
Inik
I
Chang
Soichiro
S
Yamamura
Takeshi
T
Chiyomaru
Shinichiro
S
Fukuhara
Yuichiro
Y
Tanaka
Guoren
G
Deng
Z Laura
ZL
Tabatabai
Rajvir
R
Dahiya
D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D035683:MicroRNAs / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
D035683:MicroRNAs; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases