PIK3CD promoted proliferation in diffuse large B cell lymphoma through upregulation of c-myc

Tumour Biol. 2016 Sep;37(9):12767-12777. doi: 10.1007/s13277-016-5225-5. Epub 2016 Jul 22.

Abstract

Despite PIK3CD has been extensively reported in cancers, however, little evidence has been available regarding its role in the setting of diffuse large B cell lymphoma (DLBCL). In the present study, to investigate the role of PIK3CD in DLBCL, relevant experiments were carried out on both in vivo clinical tissue level and in vitro cell line level. Prognostic and clinicopathological significance were analyzed after immunohistochemical assay of PIK3CD expression on DLBCL tissue microarray. MTT assay and flow cytometry were employed to evaluate the proliferative variation, cell cycle, and apoptosis. Athymic nude mice xenografted with DLBCL cell line were employed to confirm the role of PIK3CD. It was found that there was a significant difference between expression of PIK3CD and international prognosis index (IPI), performance state (PS), and inferior overall prognosis. Furthermore, PIK3CD can promote proliferation and prevent apoptosis in DLBCL cells in vitro through upregulation of c-myc and p-AKT and in contrast downregulation of p21 and p27. In nude mice model, knock-down of PIK3CD was shown to be able to suppress the proliferation of DLBCL but not significantly compared with control group. Taken together, our study showed that PIK3CD can promote proliferation of DLBCL cells both in vitro and in vivo, suggesting that PIK3CD could be druggable in the therapy of DLBCL.

Keywords: Diffuse large B cell lymphoma (DLBCL); PIK3CD; Prognosis; Proliferation.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Blotting, Western
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation*
  • Class I Phosphatidylinositol 3-Kinases / biosynthesis*
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Mice, Inbred NOD
  • Mice, Nude
  • Mice, SCID
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA Interference
  • Transplantation, Heterologous
  • Up-Regulation*

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Proto-Oncogene Proteins c-myc
  • Cyclin-Dependent Kinase Inhibitor p27
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CD protein, human
  • Proto-Oncogene Proteins c-akt