The tumor suppressive role of inhibin βA in diffuse large B-cell lymphoma

Leuk Lymphoma. 2018 May;59(5):1202-1212. doi: 10.1080/10428194.2017.1372574. Epub 2017 Sep 7.

Abstract

INHBA (inhibin βA), a subunit of a ligand of the transforming growth factor-β superfamily, is known to play diverse roles in various solid tumors. However, its role in hematologic malignancies remains unexplored. Here, we investigated the function of INHBA in diffuse large B-cell lymphoma (DLBCL). Both mRNA and protein levels of INHBA were significantly downregulated in primary DLBCL tissues, irrespective of germinal center B-cell-like (GCB) or non-GCB subtype, compared to those in benign tonsils. The low level of INHBA in patients with de novo DLBCL was correlated with reduced overall and progression-free survival. Ectopic expression of INHBA in DLBCL cell lines (OCI-Ly01 and SUDHL-10) resulted in reduced cell proliferation, increased spontaneous apoptosis and arrested cell cycle in vitro and suppressed xenograft tumor growth in vivo. Moreover, INHBA enhanced the chemosensitivity of DLBCL cells. Thus, our results provide novel evidence that INHBA functions as a tumor suppressor in DLBCL.

Keywords: Diffuse large B-cell lymphoma; INHBA; tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Apoptosis / drug effects
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Cycle / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic*
  • Germinal Center / drug effects
  • Germinal Center / metabolism
  • Germinal Center / pathology
  • Humans
  • Inhibin-beta Subunits / genetics
  • Inhibin-beta Subunits / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Lymphoma, Large B-Cell, Diffuse / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Prognosis
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antibiotics, Antineoplastic
  • Biomarkers, Tumor
  • inhibin beta A subunit
  • Doxorubicin
  • Inhibin-beta Subunits