Inhibitory effect and mechanisms of microRNA-146b-5p on the proliferation and metastatic potential of Caski human cervical cancer cells

Mol Med Rep. 2015 May;11(5):3955-61. doi: 10.3892/mmr.2015.3151. Epub 2015 Jan 7.

Abstract

Cervical cancer is a common cause of cancer‑associate mortality in females, and metastasis is strongly associated with failure of cervical cancer treatment. Previous studies have indicated that microRNA (miR)‑146b‑5p is involved in the inhibition of proliferation and metastasis of numerous human cancer types. The aim of the present study was to explore the inhibitory effect of miR‑156b‑5p on the proliferation and metastatic potential of Caski human cervical cancer cells, as well as to determine the mechanisms by which it proceeds. The results demonstrated that miR‑146b‑5p was able to inhibit the proliferative, invasive and adhesive potential and block the cell cycle progression of Caski human cervical cancer cells, as determined using MTS and transwell assays as well as flow cytometry. Furthermore, quantitative polymerase chain reaction and western blot analysis revealed that transfection with miR‑146b‑5p decreased the mRNA and protein expression levels of C‑X‑C chemokine receptor type 4, matrix metalloproteinase‑2 and ‑9, c‑Myc, cyclin D1 and human papilloma virus 16. In addition, the secretion levels of transforming growth factor‑β, monocyte chemoattractant protein‑1 and tumor necrosis factor‑α, the telomerase activity, the phosphorylation of c‑Jun N‑terminal protein kinase and protein kinase B and the transcriptional activities of nuclear factor‑κB, signal transducer and activator of transcription‑3 and ‑5 were reduced. However, increased levels of p27 and p53 were detected in the miR‑146b‑5p‑overexpressing Caski cells. These results indicate that miR‑146b‑5p may be a potential therapeutic strategy for the treatment of cervical cancer through regulation of cell chemotaxis and the cell cycle.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Cytokines / metabolism
  • Female
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Metastasis
  • Signal Transduction
  • Telomerase / metabolism
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • Cytokines
  • MIRN146 microRNA, human
  • MicroRNAs
  • Telomerase