Silencing of DYRK2 increases cell proliferation but reverses CAM-DR in Non-Hodgkin's Lymphoma

Int J Biol Macromol. 2015 Nov:81:809-17. doi: 10.1016/j.ijbiomac.2015.08.067. Epub 2015 Sep 2.

Abstract

DYRK2, a dual-specificity tyrosine-(Y)-phosphorylation regulated kinase gene, is involved in regulating many processes such as cell proliferation, cell differentiation and cytokinesis. DYRK2 also plays an important role in many cancers, such as breast cancer, non-small cell lung cancer and esophageal adenocarcinomas. In this study, we found that DYRK2 is associated with the proliferation of Non-Hodgkin's lymphoma (NHL) and cell adhesion mediated drug resistance (CAM-DR). Clinically, the mRNA and protein expression levels of DYRK2 are decreased in NHL tissues compared with reactive lymphoid hyperplasia tissues. Immunohistochemical analysis revealed that low expression of DYRK2 is associated with poor prognosis of NHL patients. Interestingly, knockdown of DYRK2 can promote cell proliferation via modulating cell cycle progression. Finally, we demonstrated that DYRK2 plays an important role in CAM-DR by regulating p27(Kip1) expression. Importantly, DYRK2 knockdown reverses CAM-DR in NHL. Our research suggested that DYRK2 may be a novel therapeutic target for NHL.

Keywords: Cell adhesion mediated drug resistance (CAM-DR); DYRK2; Non-Hodgkin's lymphoma (NHL); Proliferation; p27(Kip1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Adhesion*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p27
  • Disease Progression
  • Drug Resistance, Neoplasm* / genetics
  • Dyrk Kinases
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Gene Silencing*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lymphoma, Non-Hodgkin / diagnosis
  • Lymphoma, Non-Hodgkin / genetics*
  • Lymphoma, Non-Hodgkin / metabolism
  • Lymphoma, Non-Hodgkin / mortality
  • Male
  • Middle Aged
  • Phenotype
  • Phosphorylation
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Small Interfering / genetics

Substances

  • RNA, Small Interfering
  • Cyclin-Dependent Kinase Inhibitor p27
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases