Overexpression of WDR79 in non-small cell lung cancer is linked to tumour progression

J Cell Mol Med. 2016 Apr;20(4):698-709. doi: 10.1111/jcmm.12759. Epub 2016 Feb 5.

Abstract

WD-repeat protein 79 (WDR79), a member of the WD-repeat protein family, acts as a scaffold protein, participating in telomerase assembly, Cajal body formation and DNA double-strand break repair. Here, we first report that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung cancer (NSCLC). Knockdown of WDR79 significantly inhibited the proliferation of NSCLC cells in vitro and in vivo by inducing cell cycle arrest and apoptosis. WD-repeat protein 79 -induced cell cycle arrest at the G0/G1 phase was associated with the expression of G0/G1-related cyclins and cyclin-dependent kinase complexes. We also provide evidence that WDR79 knockdown induces apoptosis via a mitochondrial pathway. Collectively, these results suggest that WDR79 is involved in the tumorigenesis of NSCLC and is a potential novel diagnostic marker and therapeutic target for NSCLC.

Keywords: apoptosis; cell cycle; lung cancer; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cyclins / genetics
  • Cyclins / metabolism
  • Disease Progression
  • Female
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Mitochondria / metabolism
  • Molecular Chaperones
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Proteins / antagonists & inhibitors
  • Proteins / genetics*
  • Proteins / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Resting Phase, Cell Cycle / genetics
  • Signal Transduction
  • Telomerase
  • Xenograft Model Antitumor Assays

Substances

  • Carrier Proteins
  • Cyclins
  • ELP2 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Molecular Chaperones
  • Phosphoproteins
  • Proteins
  • RNA, Small Interfering
  • Telomerase
  • WRAP53 protein, human