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, Fei Fei Liu

Research output: Contribution to journalArticle

83 Citations (Scopus)

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 realtime 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.

Original languageEnglish
Pages (from-to)1090-1100
Number of pages11
JournalOncotarget
Volume6
Issue number2
DOIs
Publication statusPublished - 2015

All Science Journal Classification (ASJC) codes

  • Oncology

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    Kogo, R., How, C., Chaudary, N., Bruce, J., Shi, W., Hill, R. P., Zahedi, P., Yip, K. W., & Liu, F. F. (2015). The microRNA-218~Survivin axis regulates migration, invasion, and lymph node metastasis in cervical cancer. Oncotarget, 6(2), 1090-1100. https://doi.org/10.18632/oncotarget.2836