Over-Expressed miR-224 Promotes the Progression of Cervical Cancer via Targeting RASSF8

PLoS One. 2016 Sep 14;11(9):e0162378. doi: 10.1371/journal.pone.0162378. eCollection 2016.


Cervical cancer is the most common cause of cancer-related deaths in women from developing countries. Identification of novel prognostic predictors or therapeutic targets may improve patient prognosis. In the current study, we demonstrated by real-time PCR that miR-224 expression was significantly upregulated (1.82-fold, P = 0.0025) in cervical cancer tissues (n = 126) compared with in normal cervical tissues (n = 64). Higher expression of miR-224 was significantly associated with poorer prognostic factors, including advanced FIGO stage, nodal metastasis, larger tumor size, vascular involvement and deep stromal invasion (all P < 0.05). Enforced expression of miR-224 promoted cell proliferation, migration and invasion in SiHa and CaSki cancer cell lines. Bioinformatic analysis indicated that RASSF8 (RAS-association domain family 8) was a potential target of miR-224. Western blot analysis and luciferase reporter assay showed that overexpressed miR-224 inhibited RASSF8 protein expression and decreased the activity of a luciferase reporter containing the 3' untranslated region (UTR) of RASSF8, respectively. Further, RASSF8 knockdown by specific RNAi showed similar effects in cervical cancer cells transfected with miR-224 mimic. Our findings suggest that miR-224 directly targets RASSF8 and thereby acts as a tumor promoter in cervical cancer progression.

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Female
  • Humans
  • MicroRNAs / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology*


  • MIRN224 microRNA, human
  • MicroRNAs
  • RASSF8 protein, human
  • Tumor Suppressor Proteins

Grants and funding

This work was supported by National Natural Science Foundation of China (Grant No.81301687,http://www.nsfc.gov.cn) to Y. Li, Zhejiang Provincial Natural Science Foundation of China (Grant No. LQ13H160003, http://www.zjnsf.gov.cn), Ministry of Education of the People's Republic of China(Grant No.20120101110019) to X. Xie, National Natural Science Foundation of China (Grant No 81302248)to Dr Fen f Wang. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.