Upregulation of special AT-rich-binding protein 1 by Epstein-Barr virus latent membrane protein 1 in human nasopharyngeal cells and nasopharyngeal cancer

J Gen Virol. 2013 Mar;94(Pt 3):507-513. doi: 10.1099/vir.0.046243-0. Epub 2012 Dec 5.

Abstract

A global regulator of chromatin remodelling and gene expression, special AT-rich-binding protein 1 (SATB1) has been implicated in promotion of growth and metastasis of a number of cancers. Here, we demonstrate that the principal oncogene of Epstein-Barr virus (EBV), latent membrane protein 1 (LMP1) upregulates SATB1 RNA and protein expression in human nasopharyngeal cell lines. Silencing of endogenously expressed SATB1 with specific short hairpin RNA decreases cell proliferation and resistance to apoptosis induced by growth factor withdrawal. Additionally, we provide evidence that LMP1-mediated expression of Survivin, a multifunctional protein involved in promoting cell growth and survival, is mediated at least in part by SATB1 in human nasopharyngeal cells. Finally, we show that SATB1 protein levels are elevated in tissue samples from patients with nasopharyngeal carcinoma (NPC), and are directly correlated with the expression of LMP1. Taken together, our results suggest that SATB1 functions as a pro-metastatic effector of LMP1 signalling in EBV-positive NPC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma
  • Cell Line
  • Cell Proliferation
  • Gene Expression Regulation / physiology
  • Herpesvirus 4, Human / metabolism*
  • Humans
  • Matrix Attachment Region Binding Proteins / genetics
  • Matrix Attachment Region Binding Proteins / metabolism*
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / virology
  • Nose / cytology
  • Pharynx / cytology
  • RNA, Small Interfering
  • Signal Transduction
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism*

Substances

  • EBV-associated membrane antigen, Epstein-Barr virus
  • Matrix Attachment Region Binding Proteins
  • RNA, Small Interfering
  • SATB1 protein, human
  • Viral Matrix Proteins