Deregulation of lipid metabolism pathway genes in nasopharyngeal carcinoma cells

Mol Med Rep. 2013 Mar;7(3):731-41. doi: 10.3892/mmr.2012.1253. Epub 2012 Dec 28.

Abstract

Nasopharyngeal carcinoma (NPC) is a unique tumour of epithelial origin with a distinct geographical distribution, closely associated with the Epstein‑Barr virus (EBV). EBV‑encoded RNAs (EBERs) are small non‑polyadenylated RNAs that are abundantly expressed in latent EBV‑infected NPC cells. To study the role of EBERs in NPC, we established stable expression of EBERs in HK1, an EBV‑negative NPC cell line. Cells expressing EBERs consistently exhibited an increased growth rate. However, EBERs did not confer resistance towards cisplatin‑induced apoptosis or promote migration or invasion ability in the cells tested. Using microarray gene expression profiling, we identified potential candidate genes that were deregulated in NPC cells expressing EBERs. Gene Ontology analysis of the data set revealed that EBERs upregulate the cellular lipid metabolic process. Upregulation of low‑density lipoprotein receptor (LDLR) and fatty acid synthase (FASN) was observed in EBER‑expressing cells. NPC cells exhibited LDL‑dependent cell proliferation. In addition, a polyphenolic flavonoid compound, quercetin, known to inhibit FASN, was found to inhibit proliferation of NPC cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Carcinoma / drug therapy
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Fatty Acid Synthases / metabolism
  • Gene Expression Profiling
  • Herpesvirus 4, Human / metabolism
  • Humans
  • Lipid Metabolism / genetics*
  • Mice
  • Mice, Nude
  • Nasopharyngeal Neoplasms / drug therapy
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • Quercetin / pharmacology
  • RNA, Viral / metabolism
  • Receptors, LDL / metabolism
  • Transplantation, Heterologous
  • Up-Regulation / drug effects
  • Viral Matrix Proteins / metabolism

Substances

  • Antineoplastic Agents
  • RNA, Viral
  • Receptors, LDL
  • Viral Matrix Proteins
  • Quercetin
  • Fatty Acid Synthases
  • Cisplatin