The c-Jun and JunB transcription factors facilitate the transit of classical Hodgkin lymphoma tumour cells through G1

Sci Rep. 2018 Oct 30;8(1):16019. doi: 10.1038/s41598-018-34199-9.

Abstract

Classical Hodgkin Lymphoma (cHL) is primarily a B cell lymphoid neoplasm and a member of the CD30-positive lymphomas. cHL and the other CD30-positive lymphomas are characterized by the elevated expression and/or constitutive activation of the activator protein-1 (AP-1) family transcription factors, c-Jun and JunB; however, the specific roles they play in the pathobiology of cHL are unclear. In this report we show that reducing either c-Jun or JunB expression with short-hairpin RNAs (shRNAs) reduced the growth of cHL cell lines in vitro and in vivo, primarily through impairing cell cycle transition through G1. We further investigated the effect of c-Jun and JunB knock-down on proliferation in another CD30-positive lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL). We found that JunB knock-down in most ALK+ ALCL cell lines examined also resulted in reduced proliferation that was associated with a G0/G1 cell cycle defect. In contrast, c-Jun knock-down in multiple ALK+ ALCL cell lines had no effect on proliferation. In summary, this study directly establishes that both c-Jun and JunB play roles in promoting HRS cell proliferation. Furthermore, we demonstrate there are similarities and differences in c-Jun and JunB function between cHL and ALK+ ALCL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • G1 Phase Cell Cycle Checkpoints* / genetics
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Hodgkin Disease / genetics*
  • Hodgkin Disease / metabolism*
  • Hodgkin Disease / pathology
  • Humans
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*
  • RNA, Small Interfering / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • JunB protein, human
  • Proto-Oncogene Proteins c-jun
  • RNA, Small Interfering
  • Transcription Factors