MicroRNA-21 promotes proliferation, migration, and invasion of cervical cancer through targeting TIMP3

Arch Gynecol Obstet. 2018 Feb;297(2):433-442. doi: 10.1007/s00404-017-4598-z. Epub 2017 Nov 24.


Background: The expression of microRNA-21 (miR-21) is up-regulated in various cancers, including cervical cancer. However, the function of miR-21 through tissue inhibitor of metalloproteinase 3 (TIMP3) on the proliferation, migration, and invasion in cervical cancer is still unclear.

Methods: A total of 60 paired fresh cervical cancer tissues, the corresponding adjacent non-neoplastic tissues and serum samples were collected from cervical cancer patients, while 60 matched normal tissues and serum samples were collected from the control group. MiR-21 expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). TIMP3 expression was evaluated by Western blot and qRT-PCR. Cell proliferation was determined by MTT assay. Migratory and invasive activities were assessed by cell migration and invasion assays, respectively. Luciferase reporter assay was employed to validate the direct targeting of TIMP3 by miR-21.

Results: MiR-21 was up-regulated in cervical cancer tissues and serum samples, in contrast, TIMP3 was down-regulated in cervical cancer tissues. MiR-21 promoted the proliferation, viability and the migratory and invasive activities of cervical cancer cells through targeting TIMP3. Overexpression of TIMP3 attenuated the positive effects of miR-21.

Conclusions: These findings provide a novel insight into the molecular functions of miR-21 in cervical cancer, which may be used as a diagnostic and prognostic biomarker for the treatment of cervical cancer in the future.

Keywords: Cervical cancer; Invasion; MiR-21; Migration; Proliferation; TIMP3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Movement / physiology
  • Cell Proliferation / genetics*
  • Cell Proliferation / physiology
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Real-Time Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-3 / genetics*
  • Up-Regulation
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology


  • MIRN21 microRNA, human
  • MicroRNAs
  • TIMP3 protein, human
  • Tissue Inhibitor of Metalloproteinase-3