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-regulat...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3464246?pdf=render |
| _version_ | 1818288311969513472 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shahana Majid |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T01:54:22Z |
| format | Article |
| id | doaj.art-8eddfd455746402583d972da74ca2262 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T01:54:22Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-8eddfd455746402583d972da74ca22622022-12-22T00:03:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4674310.1371/journal.pone.0046743MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer.Shahana MajidAltaf A DarSharanjot SainiVarahram ShahryariSumit AroraMohd Saif ZamanInik ChangSoichiro YamamuraTakeshi ChiyomaruShinichiro FukuharaYuichiro TanakaGuoren DengZ Laura TabatabaiRajvir DahiyaMicroRNAs (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.http://europepmc.org/articles/PMC3464246?pdf=render |
| spellingShingle | 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 MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer. PLoS ONE |
| title | MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer. |
| title_full | MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer. |
| title_fullStr | MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer. |
| title_full_unstemmed | MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer. |
| title_short | MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer. |
| title_sort | microrna 1280 inhibits invasion and metastasis by targeting rock1 in bladder cancer |
| url | http://europepmc.org/articles/PMC3464246?pdf=render |
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