A novel oncogenic pathway by TLS-CHOP involving repression of MDA-7/IL-24 expression

Br J Cancer. 2012 Jun 5;106(12):1976-9. doi: 10.1038/bjc.2012.199. Epub 2012 May 15.

Abstract

Background: Translocated in liposarcoma-CCAAT/enhancer binding protein homologous protein (TLS-CHOP) (also known as FUS-DDIT3) chimeric oncoprotein is found in the majority of human myxoid liposarcoma (MLS), but its molecular function remains unclear.

Methods: We knockdowned TLS-CHOP expression in MLS-derived cell lines by a specific small interfering RNA, and analysed the gene expression profiles with microarray.

Results: TLS-CHOP knockdown inhibited growth of MLS cells, and induced an anticancer cytokine, melanoma differentiation-associated gene 7 (MDA-7)/interleukin-24 (IL-24) expression. However, double knockdown of TLS-CHOP and MDA-7/IL-24 did not inhibit MLS cell growth.

Conclusion: Repression of MDA-7/IL-24 expression by TLS-CHOP is required for MLS tumour growth, and TLS-CHOP may become a promising therapeutic target for MLS treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • Humans
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Liposarcoma, Myxoid / genetics
  • Liposarcoma, Myxoid / metabolism*
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism*
  • RNA-Binding Protein FUS / genetics
  • RNA-Binding Protein FUS / metabolism*
  • Transcription Factor CHOP / genetics
  • Transcription Factor CHOP / metabolism*

Substances

  • Interleukins
  • Oncogene Proteins, Fusion
  • RNA-Binding Protein FUS
  • TLS-CHOP fusion protein, human
  • interleukin-24
  • Transcription Factor CHOP