MicroRNA-211, a direct negative regulator of CDC25B expression, inhibits triple-negative breast cancer cells' growth and migration

Tumour Biol. 2015 Jul;36(7):5001-9. doi: 10.1007/s13277-015-3151-6. Epub 2015 Feb 14.

Abstract

The non-coding microRNAs (miRNAs) have tissue- and disease-specific expression patterns. Dysregulation of miRNAs has been associated with initiation and progression of oncogenesis in humans. The abnormal expression of CDC25B phosphatases detected in a number of tumors implies that their dysregulation is involved in malignant transformation. Using miRNA target prediction software, we found that miR-211 could target the 3'UTR sequence of CDC25B. To shed light on their roles of miR-211 in breast cancer, the expression of miR-211 was examined by real-time RT-PCR in breast cancer and normal tissues. MiR-211 is significantly downregulated in breast cancer. MiR-211 re-expression suppressed cell growth, cell cycle, migration, and invasion in triple-negative breast cancer (TNBC) cell line MDA-MB231. Luciferase expression from a reporter vector containing the CDC25B -3'UTR was decreased when this construct was transfected with miR-211. The over-expression of miR-211 suppressed the endogenous CDC25B protein level in TNBC cells. For the first time, we demonstrate that miRNA-211 is a direct negative regulator of CDC25B expression in TNBC cells, alters other related target proteins CCNB1 and FOXM1, and then inhibits breast cancer cells growth, migration, and invasion and lead G2/M arrest. The transcriptional loss of miR-211 and the resultant increase in CDC25B expression facilitate increased genomic instability at an early stage of tumor development.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Cyclin B1 / biosynthesis
  • Cyclin B1 / genetics
  • Female
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness / genetics
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology
  • cdc25 Phosphatases / biosynthesis*
  • cdc25 Phosphatases / genetics

Substances

  • CCNB1 protein, human
  • Cyclin B1
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • MIRN211 microRNA, human
  • MicroRNAs
  • CDC25B protein, human
  • cdc25 Phosphatases