MicroRNA-183 functions as the tumor suppressor via inhibiting cellular invasion and metastasis by targeting MMP-9 in cervical cancer

Gynecol Oncol. 2016 Apr;141(1):166-74. doi: 10.1016/j.ygyno.2016.02.006. Epub 2016 Feb 9.

Abstract

Objective: MicroRNAs have been reported to play an important role in the invasion and metastasis of cervical cancer. miR-183 was found to inhibit or promote the invasion and metastasis of multiple solid tumors. However, the roles of miR-183 in cervical cancer are unclear.

Methods: In this study, miR-183 expression levels were measured in 53 cervical cancer and 13 normal cervical tissues by qRT-PCR. The effects of forced expression of miR-183 on cervical cancer cells invasion and metastasis were investigated using Transwell uncoated or coated with growth factor-reduced Matrigel for migration or invasion assays, respectively.

Results: We found that miR-183 expression levels were significantly down-regulated in cervical cancer tissues compared with normal tissues (0.15±0.011 to 0.86±0.049). Ectopic expression of miR-183 resulted in the suppression of invasion and migration of cervical cancer cell lines, siha and Hela cells (p<0.0001). Bioinformatics analysis revealed that MMP-9 was the potential target of miR-183 and it was found that MMP-9 was remarkably up-regulated in cervical cancer. Furthermore, a dual-luciferase reporter assay showed that MMP-9 as a target of miR-183 (p<0.0001). The invasion and metastasis ability of siha and Hela was suppressed when MMP-9 was down-regulated in vitro (p<0.0001).

Conclusions: In conclusion, our study revealed that miR-183 might be a tumor suppressor via inhibiting the invasion and metastasis of cervical cancer cells through targeting MMP-9, indicating that miR-183 may be a novel potential therapeutic target for cervical cancer.

Keywords: Cervical cancer; Invasion; MMP-9; Metastasis; miR-183.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Computational Biology
  • Female
  • Genes, Tumor Suppressor / physiology*
  • Humans
  • Matrix Metalloproteinase 9 / analysis
  • Matrix Metalloproteinase 9 / genetics*
  • MicroRNAs / analysis
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology*

Substances

  • MIRN183 microRNA, human
  • MicroRNAs
  • MMP9 protein, human
  • Matrix Metalloproteinase 9