Circulating MicroRNA-21 Is Involved in Lymph Node Metastasis in Cervical Cancer by Targeting RASA1

Int J Gynecol Cancer. 2016 Jun;26(5):810-6. doi: 10.1097/IGC.0000000000000694.


The aims of this study were to discover if increased circulating microRNA-21 (miR-21) expression in serum is associated with lymph node metastasis in patients with cervical cancer and look further into the molecular mechanism of these. Whole-blood samples from 89 patients who have been histopathologically confirmed as having cervical cancer and 20 control subjects were collected, and then the association between lymph node metastasis and the level of circulating miR-21 was compared. Then cervical cancer cell lines HeLa (HPV-18 DNA, E6/E7RNA) and HT-3 (HPV DNA, E6/E7RNA) were used to confirm the interaction between miR-21 and RASA1. The role of RASA1 in cervical cancer cell migration was also studied in HeLa. Increased circulating miR-21 expression in serum is associated with lymph node metastasis in patients with cervical cancer. MicroRNA-21 reduces RASA1 expression in cervical cancer cell lines and promotes cervical cancer cell migration via RASA1. Furthermore, Ras-induced epithelial-mesenchymal transition contributes to miR-21/RASA1 axis promoting cervical cancer cell migration. Circulating miR-21 in serum could be a promising biomarker in auxiliary diagnosis of lymph node metastasis in cervical cancer, and inhibition of miR-21/RASA1 axis could be a possible strategy to restrain migration of cervical cancer.

MeSH terms

  • Case-Control Studies
  • Cell Movement / genetics
  • Epithelial-Mesenchymal Transition
  • Female
  • HeLa Cells
  • Humans
  • Lymphatic Metastasis
  • MicroRNAs / biosynthesis
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Middle Aged
  • Prognosis
  • Uterine Cervical Neoplasms / blood
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*
  • p120 GTPase Activating Protein / blood*
  • p120 GTPase Activating Protein / genetics


  • MIRN21 microRNA, human
  • MicroRNAs
  • RASA1 protein, human
  • p120 GTPase Activating Protein