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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere46743
JournalPloS one
Volume7
Issue number10
DOIs
StatePublished - Oct 4 2012

Fingerprint

MicroRNAs
microRNA
Urinary Bladder Neoplasms
metastasis
Cells
Neoplasm Metastasis
Tumors
cell lines
oncogenes
Oncogenes
Cell Line
neoplasms
urinary bladder neoplasms
G2 Phase Cell Cycle Checkpoints
Luciferases
Sorting
Neoplasms
Restoration
tumor suppressor genes
Assays

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Majid, S., Dar, A. A., Saini, S., Shahryari, V., Arora, S., Zaman, M. S., ... Dahiya, R. (2012). MicroRNA-1280 Inhibits Invasion and Metastasis by Targeting ROCK1 in Bladder Cancer. PloS one, 7(10), [e46743]. https://doi.org/10.1371/journal.pone.0046743

MicroRNA-1280 Inhibits Invasion and Metastasis by Targeting ROCK1 in Bladder Cancer. / Majid, Shahana; Dar, Altaf A.; Saini, Sharanjot; Shahryari, Varahram; Arora, Sumit; Zaman, Mohd Saif; Chang, Inik; Yamamura, Soichiro; Chiyomaru, Takeshi; Fukuhara, Shinichiro; Tanaka, Yuichiro; Deng, Guoren; Tabatabai, Z. Laura; Dahiya, Rajvir.

In: PloS one, Vol. 7, No. 10, e46743, 04.10.2012.

Research output: Contribution to journalArticle

Majid, S, Dar, AA, Saini, S, Shahryari, V, Arora, S, Zaman, MS, Chang, I, Yamamura, S, Chiyomaru, T, Fukuhara, S, Tanaka, Y, Deng, G, Tabatabai, ZL & Dahiya, R 2012, 'MicroRNA-1280 Inhibits Invasion and Metastasis by Targeting ROCK1 in Bladder Cancer', PloS one, vol. 7, no. 10, e46743. https://doi.org/10.1371/journal.pone.0046743
Majid S, Dar AA, Saini S, Shahryari V, Arora S, Zaman MS et al. MicroRNA-1280 Inhibits Invasion and Metastasis by Targeting ROCK1 in Bladder Cancer. PloS one. 2012 Oct 4;7(10). e46743. https://doi.org/10.1371/journal.pone.0046743
Majid, Shahana ; Dar, Altaf A. ; Saini, Sharanjot ; Shahryari, Varahram ; Arora, Sumit ; Zaman, Mohd Saif ; Chang, Inik ; Yamamura, Soichiro ; Chiyomaru, Takeshi ; Fukuhara, Shinichiro ; Tanaka, Yuichiro ; Deng, Guoren ; Tabatabai, Z. Laura ; Dahiya, Rajvir. / MicroRNA-1280 Inhibits Invasion and Metastasis by Targeting ROCK1 in Bladder Cancer. In: PloS one. 2012 ; Vol. 7, No. 10.
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