Frequent Nek1 overexpression in human gliomas

Biochem Biophys Res Commun. 2016 Aug 5;476(4):522-527. doi: 10.1016/j.bbrc.2016.05.156. Epub 2016 May 29.

Abstract

Never in mitosis A (NIMA)-related kinase 1 (Nek1) regulates cell cycle progression to mitosis. Its expression and potential functions in human gliomas have not been studied. Here, our immunohistochemistry (IHC) assay and Western blot assay results showed that Nek1 expression was significantly upregulated in fresh and paraffin-embedded human glioma tissues. Its level in normal brain tissues was low. Nek1 overexpression in human gliomas was correlated with the proliferation marker (Ki-67), tumor grade, Karnofsky performance scale (KPS) and more importantly, patients' poor survival. Further studies showed that Nek1 expression level was also increased in multiple human glioma cell lines (U251-MG, U87-MG, U118, H4 and U373). Significantly, siRNA-mediated knockdown of Nek1 inhibited glioma cell (U87-MG/U251-MG) growth. Nek1 siRNA also sensitized U87-MG/U251-MG cells to temozolomide (TMZ), causing a profound apoptosis induction and growth inhibition. The current study indicates Nek1 might be a novel and valuable oncotarget of glioma, it is important for glioma cell growth and TMZ-resistance.

Keywords: Glioma; Nek1; Oncotarget; Proliferation; Temozolomide (TMZ).

MeSH terms

  • Adult
  • Antineoplastic Agents, Alkylating / pharmacology
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / pharmacology
  • Drug Resistance, Neoplasm
  • Female
  • Gene Knockdown Techniques
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • NIMA-Related Kinase 1 / antagonists & inhibitors
  • NIMA-Related Kinase 1 / genetics
  • NIMA-Related Kinase 1 / metabolism*
  • Temozolomide
  • Tumor Stem Cell Assay
  • Up-Regulation

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • NEK1 protein, human
  • NIMA-Related Kinase 1
  • Temozolomide