Oncotarget

Research Papers:

The microRNA-218~Survivin axis regulates migration, invasion, and lymph node metastasis in cervical cancer

Ryunosuke Kogo, Christine How, Naz Chaudary, Jeff Bruce, Wei Shi, Richard P. Hill, Payam Zahedi, Kenneth W. Yip and Fei-Fei Liu _

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Oncotarget. 2015; 6:1090-1100. https://doi.org/10.18632/oncotarget.2836

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Abstract

Ryunosuke Kogo1, Christine How1, Naz Chaudary1, Jeff Bruce1, Wei Shi1, Richard P. Hill1,2,3, Payam Zahedi1, Kenneth W. Yip1 and Fei-Fei Liu1,2,3,4

1 Ontario Cancer Institute, University Health Network (UHN), Toronto, Ontario, Canada

2 Department of Medical Biophysics, University of Toronto, Toronto, Canada

3 Department of Radiation Oncology, University of Toronto, Toronto, Canada

4 Department of Radiation Oncology, Princess Margaret Cancer Centre, UHN, Toronto, Canada

Correspondence:

Fei-Fei Liu, email:

Keywords: miR-218, survivin, cervical cancer, migration, invasion

Received: September 30, 2014 Accepted: November 24, 2014 Published: November 25, 2014

Abstract

Cervical cancer is the third most common cancer in women worldwide. In the present study, global microRNA profiling for 79 cervical cancer patient samples led to the identification of miR-218 down-regulation in cervical cancer tissues compared to normal cervical tissues. Lower miR-218 expression was associated significantly with worse overall survival (OS), disease-free survival (DFS), and pelvic/aortic lymph node recurrence. In vitro, miR-218 over-expression decreased clonogenicity, migration, and invasion. Survivin (BIRC5) was subsequently identified as an important cervical cancer target of miR-218 using in silico prediction, mRNA profiling, and quantitative real-time PCR (qRT-PCR). Concordant with miR-218 over-expression, survivin knockdown by siRNA decreased clonogenicity, migration, and invasion. YM155, a small molecule survivin inhibitor, significantly suppressed tumor growth and lymph node metastasis in vivo. Our findings demonstrate that the miR-218~survivin axis inhibits cervical cancer progression by regulating clonogenicity, migration, and invasion, and suggest that the inhibition of survivin could be a potential therapeutic strategy to improve outcome in this disease.


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