Downregulation of PRDM1 promotes cellular invasion and lung cancer metastasis

Tumour Biol. 2017 Apr;39(4):1010428317695929. doi: 10.1177/1010428317695929.

Abstract

The zinc-finger transcription factor PRDM1 (PR domain containing 1) plays key roles in the development of malignant lymphoma, leukaemia and some non-haematopoietic cancers, including breast cancer, colorectal cancer and glioma. However, little is known regarding the function of PRDM1 in the progression of lung cancer. Here, we found that PRDM1 is expressed in normal human lung epithelium but is downregulated in lung cancer cells. Decreased expression of PRDM1 correlates with poor prognosis in lung cancer. Depletion of PRDM1 in lung cancer cells promotes cellular invasion and anoikis resistance in vitro and lung metastasis in vivo. PRDM1 is silenced by an ectopically expressed lymphocyte-specific transcription factor Aiolos. The transcription of these two genes is negatively correlated in 206 lung epithelial cell lines. Our results indicate that PRDM1 functions as a tumour suppressor in lung cancer.

Keywords: PRDM1; gene silencing; lung cancer; metastasis; transcriptional regulation.

MeSH terms

  • Animals
  • Anoikis
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cells, Cultured
  • Down-Regulation
  • Female
  • Fibronectins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ikaros Transcription Factor / metabolism
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Positive Regulatory Domain I-Binding Factor 1
  • Prognosis
  • Repressor Proteins / metabolism*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Fibronectins
  • IKZF3 protein, human
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • PRDM1 protein, human
  • Ikaros Transcription Factor
  • Positive Regulatory Domain I-Binding Factor 1
  • Caspases