miR-376c inhibits cervical cancer cell proliferation and invasion by targeting BMI1

Int J Exp Pathol. 2016 Jun;97(3):257-65. doi: 10.1111/iep.12177. Epub 2016 Jun 27.


MicroRNAs (miRNAs) play crucial roles in cancer development and progression. The purposes of this study were to explore the role of miR-376c in cervical cancer and to clarify the regulation of BMI1 by miR-376c. Quantitative RT-PCR was used to measure miR-376c expression in cervical cancer tissues and cell lines. The cell proliferation, cell cycle and Transwell invasion assays were performed. A luciferase reporter assay was conducted to confirm the target gene of miR-376c, and the results were validated in cervical cancer cell lines and tissues. MiR-376c was significantly downregulated in cervical cancer cell lines and clinical tissues. Upregulation of miR-376c impaired cell proliferation, blocked G1/S checkpoint of cell cycle and suppressed cell invasion in vitro. BMI1 was verified as a direct target of miR-376c, which was further confirmed by the inverse expression of miR-376c and BMI1 in patient specimens. The newly identified miR-376c/BMI1 pathway provides an insight into cervical cancer progression and may represent a novel therapeutic target.

Keywords: BMI1; Cervical cancer; HPV; miR-376c.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics*
  • Polycomb Repressive Complex 1 / metabolism*
  • Up-Regulation
  • Uterine Cervical Neoplasms / genetics*


  • BMI1 protein, human
  • MIRN376C microRNA, human
  • MicroRNAs
  • Polycomb Repressive Complex 1