Pax-5 Inhibits Breast Cancer Proliferation Through MiR-215 Up-regulation

Anticancer Res. 2018 Sep;38(9):5013-5026. doi: 10.21873/anticanres.12820.

Abstract

Background/aim: In breast cancer, Pax-5 promotes pro-epithelial features and suppresses malignant cancer processes. However, the molecular mechanism of this antitumor activity remains largely unknown. This study aimed to identify the cellular roles of Pax-5-regulated miRNAs in breast cancer progression.

Materials and methods: After transient transfection of Pax-5 in MDA-MB-231 breast cancer cells, Pax-5-regulated miRNA expression was examined by next-generation sequencing. The identified Pax-5-regulated miRNAs were then validated by qRT-PCR and examined for the roles they play in breast cancer cells.

Results: Pax-5 was shown to be an effective modulator of miR-215-5p and its target genes. MiR-215 inhibited cell proliferation and migration of breast cancer cells, but not cell invasion. More importantly, Pax-5-induced suppression of cancer cell proliferation and migration was found to be miR-215-dependent. Interestingly, miR-215 profiling in clinical tumor samples showed that miR-215 expression was lower in cancer tissues in comparison to healthy controls.

Conclusion: Pax-5 reduces breast cancer proliferation and migration through up-regulation of the tumor suppressor miR-215. This result supports the use of miR-215 as a prognostic marker for breast cancer.

Keywords: EMT/MET; Pax-5; breast cancer; miR-215-5p; miRNA.

MeSH terms

  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • High-Throughput Nucleotide Sequencing
  • Humans
  • MicroRNAs / genetics*
  • PAX5 Transcription Factor / genetics*
  • Sequence Analysis, RNA
  • Up-Regulation*

Substances

  • MIRN215 microRNA, human
  • MicroRNAs
  • PAX5 Transcription Factor
  • PAX5 protein, human