Downregulation of NUF2 inhibits tumor growth and induces apoptosis by regulating lncRNA AF339813

Int J Clin Exp Pathol. 2015 Mar 1;8(3):2638-48. eCollection 2015.

Abstract

Recent studies have shown that NUF2 (Ndc80 kinetochore complex component) play important roles in multiple human cancers. In our previous report, NUF2 expression was stronger in tumor tissues than in normal pancreatic tissues. However, whether and how NUF2 play a role in pancreatic cancer progression remains largely unknown. The aim of our study is to investigate the expression and functional role of NUF2 in human PC. NUF2 expression was measured in 10 pairs of PC cancerous and noncancerous tissue samples by quantitative real-time PCR. The effects of NUF2 on PC cells were studied by RNA interference. Apoptosis and cell cycle were analyzed by flow cytometry. Cells viability was evaluated using MTT. CDK4/CDK6 activity was measured by Western blot assay. LncRNAs regulated by NUF2 were gained from bioinformatics analysis. The role of LncRNA AF339813, regulated by NUF2, was finally characterized in PC cells by siRNA. Our results showed that NUF2 mRNA and protein were significantly overexpressed in Human PC tissues and several PC cell lines. Through bioinformatics analysis and knockdown NUF2 in PC cells, we found LncRNA AF339813 was positively regulated by NUF2. We further demonstrated that knockdown of AF339813 by siRNA in PC cells significantly reduced cell proliferation and promoted apoptosis. Thus, we conclude that NUF2 is consistently overexpressed in human PC and NUF2 is closely linked with human PC progression through the meditator LncRNA AF339813. Our studies may contribute to understand the molecular mechanism of PC pathogenesis and clinical therapy.

Keywords: LncRNA AF339813; NUF2; RNA interference; pancreatic cancer.

MeSH terms

  • Apoptosis / physiology*
  • Blotting, Western
  • Cell Cycle Proteins / biosynthesis*
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering
  • Real-Time Polymerase Chain Reaction
  • Transfection

Substances

  • AF339813 long non-coding RNA, human
  • Cell Cycle Proteins
  • NUF2 protein, human
  • RNA, Long Noncoding
  • RNA, Small Interfering