SUZ12 depletion suppresses the proliferation of gastric cancer cells

Cell Physiol Biochem. 2013;31(6):778-84. doi: 10.1159/000350095. Epub 2013 May 31.

Abstract

Background/aims: SUZ12 and EZH2 are two main components of polycomb repressive complex 2 (PRC2) that is known to be of great importance in tumorigenesis. EZH2 has been reported to play a vital role in pathogenesis of human cancer. However, whether SUZ12 has equivalent roles in tumorigenesis has not been demonstrated. Here, we investigated a possible role of SUZ12 for the proliferation of gastric cancer cells.

Methods: Western-blot analysis was used to detected the levels of SUZ12, H3K27me3, EZH2 and p27 in ten gastric cell lines. SUZ12 was depleted by RNA interference. Cell cycle was detected by flow cytometry. Luciferase assays was to analyze whether miR-200b directly regulate SUZ12.

Results: We found that SUZ12 depletion mediated by RNA interference (RNAi) led to a reduction of gastric cell numbers and arrested the cell cycle at G1/S point. As an important G1/S phase inhibitory gene, p27 is re-induced to some extent by SUZ12 knockdown. Furthermore, we demonstrated that SUZ12 was directly downregulated by miR-200b.

Conclusion: We provide evidence suggesting that SUZ12 may be a potential therapeutic target for gastric cancer.

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Down-Regulation
  • G1 Phase Cell Cycle Checkpoints
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • MicroRNAs / chemistry
  • MicroRNAs / metabolism
  • Neoplasm Proteins
  • Polycomb Repressive Complex 2 / antagonists & inhibitors
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • S Phase Cell Cycle Checkpoints
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Transcription Factors

Substances

  • Histones
  • MIRN200 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Small Interfering
  • SUZ12 protein, human
  • Transcription Factors
  • Cyclin-Dependent Kinase Inhibitor p27
  • Polycomb Repressive Complex 2