The reciprocal interplay between TNFα and the circadian clock impacts on cell proliferation and migration in Hodgkin lymphoma cells

Sci Rep. 2018 Jul 31;8(1):11474. doi: 10.1038/s41598-018-29847-z.


A bidirectional interaction between the circadian network and effector mechanisms of immunity brings on a proper working of both systems. In the present study, we used Hodgkin lymphoma (HL) as an experimental model for a type of cancer involving cells of the immune system. We identified this cancer type among haematological malignancies has having a strong differential expression of core-clock elements. Taking advantage of bioinformatics analyses and experimental procedures carried out in III- and IV-stage HL cells, and lymphoblastoid B cells, we explored this interplay and bear out diverse interacting partners of both systems. In particular, we assembled a wide-ranging network of clock-immune-related genes and pinpointed TNF as a crucial intermediary player. A robust circadian clock hallmarked III-stage lymphoma cells, differently from IV-stage HL cells, which do not harbour a properly functioning clockwork. TNF and circadian gene modulation impacted on clock genes expression and triggered phenotypic changes in lymphoma cells, suggesting a crucial involvement of core-clock elements and TNF in the physiopathological mechanisms hastening malignancy. Our results move forward our understanding of the putative role of the core-clock and TNF in the pathobiology of Hodgkin lymphoma, and highlight their influence in cellular proliferation and migration in lymphatic cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Circadian Clocks / genetics*
  • Circadian Rhythm / genetics
  • Gene Expression / genetics
  • Gene Regulatory Networks / genetics
  • HEK293 Cells
  • Hodgkin Disease / genetics*
  • Humans
  • Male
  • Tumor Necrosis Factor-alpha / genetics*


  • Tumor Necrosis Factor-alpha