Upregulation of microRNA-224 is associated with aggressive progression and poor prognosis in human cervical cancer

Diagn Pathol. 2013 Apr 30:8:69. doi: 10.1186/1746-1596-8-69.


Objective: Accumulating evidence for differential expression of microRNA-224 (miR-224) in various types of human cancer suggests that it may be play a crucial role in tumor biology. The previous microarray detection also shown that miR-224 was one of miRNAs with significant upregulation in cervical cancer tissues relative to adjacent normal tissues. However, little is known about the function of miR-224 in human cervical cancer. The aim of this study was to investigate the clinical significance of miR-224 expression in cervical cancer.

Methods: MiR-224 expression in 126 pairs of fresh human cervical cancer and adjacent normal tissues was measured by real-time quantitative RT-PCR assay.

Results: miR-224 expression was significantly upregulated in cervical cancer tissues when compared with corresponding adjacent normal tissues (P<0.001). It was also significantly higher in the cancerous tissues of patients with advanced FIGO stage cervical cancer than those with early FIGO stage (P=0.02). In addition, miR-224 was expressed at significantly higher levels in lymph node metastasis-positive patients than in lymph node metastasis-negative patients (P=0.008). Moreover, we found that lesser differentiated tumors expressed higher miR-224 (P=0.03). Finally, there were sufficient evidence to confirm its value in the status of vascular invasion (P=0.01) and human papillomavirus (HPV) infection (P=0.02) in cervical cancer. More importantly, Kaplan-Meier analysis showed that cervical cancer patients with high miR-224 expression tend to have shorter overall survival. In multivariate analysis stratified for known prognostic variables, miR-224 was identified as an independent prognostic marker.

Conclusion: Our data indicated that miR-224 upregulation was associated with aggressive progression and poor prognosis in cervical cancer. MiR-224 was identified for the first time as an independent marker for predicting the clinical outcome of cervical cancer patients.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2170449349527493.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Up-Regulation / physiology
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology


  • Biomarkers, Tumor
  • MIRN224 microRNA, human
  • MicroRNAs