Tumor-specific RNA interference targeting Pokemon suppresses tumor growth and induces apoptosis in prostate cancer

Urology. 2013 Feb;81(2):467.e1-7. doi: 10.1016/j.urology.2012.10.011.

Abstract

Objective: To explore the exact mechanism of Pokemon in prostate cancer.

Materials and methods: Pokemon is a member of the POK family of transcriptional repressors. Its main function is suppression of the p14ARF (alternate reading frame) tumor suppressor gene. Although Pokemon expression has been found to be increased in various types of lymphoma, the exact mechanism of the gene in prostate cancer is not clear. In the present study, prostate cancer cells were transfected with the specific short hairpin ribonucleic acid (RNA) expression vector targeting Pokemon. The expression of Pokemon messenger RNA and its protein was detected by semiquantitative reverse transcriptase-polymerase chain reaction and Western blotting, respectively. The cell growth and cell apoptosis were also examined using the methyl thiazolyl tetrazolium assay and flow cytometry.

Results: The results demonstrated that specific RNA interference (RNAi) could decrease the expression levels of Pokemon gene messenger RNA and protein in prostate cancer cells. In addition, that specific RNAi significantly inhibited the cell proliferation and increased the apoptotic rate. In vivo experiments showed that specific RNAi inhibited the tumorigenicity of prostate cancer cells and significantly suppressed tumor growth.

Conclusion: Therefore, an RNAi-targeted Pokemon gene strategy could be a potential approach to prostate cancer therapy.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenoviridae
  • Animals
  • Apoptosis
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins / antagonists & inhibitors*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Down-Regulation*
  • Genetic Vectors
  • Humans
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasm Transplantation
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • RNA Interference*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics*
  • Transcription Factors / antagonists & inhibitors*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Transcription Factors
  • ZBTB7A protein, human
  • Caspase 3