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

Oncotarget. 2015 Jan 20;6(2):1090-100. doi: 10.18632/oncotarget.2836.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Imidazoles / pharmacology
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / metabolism
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Mice, SCID
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Naphthoquinones / pharmacology
  • Neoplasm Invasiveness
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survivin
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Xenograft Model Antitumor Assays


  • 3' Untranslated Regions
  • BIRC5 protein, human
  • Imidazoles
  • Inhibitor of Apoptosis Proteins
  • MIRN218 microRNA, human
  • MicroRNAs
  • Naphthoquinones
  • Survivin
  • sepantronium