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EBV down-regulates COX-2 expression via TRAF2 and ERK signal pathway in EBV-associated gastric cancer

Yi-Fan Qi1, Mengyang Liu2, Yan Zhang3

  • 1Department of Medical microbiology, School of Basic Medicine, Qingdao University, 38 Dengzhou Road, Qingdao, 266021, China.

Virus Research
|September 2, 2019
PubMed

Insights

Epstein-Barr virus (EBV) proteins LMP1 and LMP2A inhibit COX-2 expression in gastric cancer. This inhibition is mediated by reduced TRAF2 levels and involves p-ERK signaling, offering insights into EBV-associated gastric cancer mechanisms.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Epstein-Barr virus-associated gastric cancer (EBVaGC) comprises nearly 10% of gastric cancer cases.
  • Cyclooxygenase-2 (COX-2) is a key factor in cancer progression.
  • The regulatory mechanisms of EBV on COX-2 in EBVaGC remain experimentally underexplored.

Purpose of the Study:

  • To investigate the role of EBV-encoded latent membrane proteins (LMP1 and LMP2A) in regulating COX-2 expression in EBVaGC.
  • To elucidate the molecular pathways involved in EBV-mediated COX-2 regulation.

Main Methods:

  • Examined COX-2 expression in EBVaGC and EBV-negative gastric cancer cell lines.
  • Utilized plasmid transfection for LMP1/2A overexpression in SGC7901 cells.
  • Employed small interfering RNA (siRNA) to knockdown LMP1/2A in GT38 cells and TRAF2 in SGC7901 cells.
  • Investigated the involvement of the ERK pathway using siRNA against ERK1/2 and a MEK inhibitor (PD0325901).

Main Results:

  • Overexpression of LMP1 or LMP2A in SGC7901 cells led to down-regulation of both COX-2 and TRAF2.
  • Knockdown of LMP1 or LMP2A in GT38 cells partially restored COX-2 and TRAF2 expression.
  • siRNA targeting TRAF2 significantly down-regulated COX-2 expression.
  • A decrease in phosphorylated ERK (p-ERK) mediated the inhibitory effect of LMP1 on COX-2.

Conclusions:

  • EBV-encoded LMP1 and LMP2A inhibit COX-2 expression in gastric cancer.
  • This inhibition is mediated by a reduction in TRAF2 expression.
  • The p-ERK signaling pathway is implicated in LMP1-induced COX-2 inhibition in gastric cancer.
Keywords:
COX-2EBVaGCLMP1LMP2ATRAF2

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