MiR-195 Suppresses Cervical Cancer Migration and Invasion Through Targeting Smad3

Int J Gynecol Cancer. 2016 Jun;26(5):817-24. doi: 10.1097/IGC.0000000000000686.

Abstract

Objective: MicroRNAs (miRNAs) play crucial roles in cervical cancer development and progression. The purposes of this study were to investigate the role of miR-195 in cervical cancer and clarify the regulation of Smad3 by miR-195.

Methods: Quantitative real-time polymerase chain reaction was used to examine miR-195 expression in cervical cancer tissues and cell lines. The clinicopathological significance of miR-195 down-regulation was further analyzed. Transwell migration and invasion assays were performed. A luciferase reporter assay was conducted to confirm the target gene of miR-195, and the results were validated in cervical cancer tissues and cell lines.

Results: MiR-195 was significantly decreased in clinical tissues and cervical cancer cell lines. The low miR-195 level was significantly correlated with higher International Federation of Gynecology and Obstetrics stage, node metastasis, and deep stromal invasion. Up-regulation of miR-195 suppressed cell migration and invasion in vitro. Smad3 was verified as a direct target of miR-195, which was further confirmed by the inverse expression of miR-195 and Smad3 in patients' specimens.

Conclusions: The newly identified miR-195/Smad3 pathway provides an insight into cervical cancer metastasis and may represent a novel therapeutic target.

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Disease Progression
  • Female
  • HeLa Cells
  • Humans
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Smad3 Protein / biosynthesis
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology*

Substances

  • MIRN195 microRNA, human
  • MicroRNAs
  • SMAD3 protein, human
  • Smad3 Protein