EBV Rta-induced IL-6 Promotes Migration of Bystander Tumor Cells Through IL-6R/JAK/STAT3 Pathway In Vitro

Anticancer Res. 2020 Jun;40(6):3255-3264. doi: 10.21873/anticanres.14307.

Abstract

Background/aim: Rta, a transactivator of Epstein-Barr virus, is associated with progression of nasopharyngel carcinoma (NPC); however, its mechanism of contribution to the pathogenesis of NPC remains unclear. Interleukin-6 (IL-6), a tumor promoter, is detected in NPC. This in vitro study examined whether and how Rta promotes NPC progression by up-regulating IL-6.

Materials and methods: Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time PCR, ELISA, immunoblotting assays, reporter gene assays, and transwell migration assays were performed.

Results: In NPC cells, Rta up-regulated IL-6 expression at the mRNA and protein levels, and the Rta's C-terminus was essential for promoter activation and expression of IL-6. The induction of IL-6 by Rta also required activation of extracellular signal-regulated kinase 1/2 and activator protein-1. Furthermore, IL-6 secreted from Rta-expressing NPC cells promoted migration of Rta-negative NPC cells by activating IL-6 receptor/Janus kinase/signal transducer and activator of transcription 3 pathway.

Conclusion: Rta contributes to progression of NPC cells through induction of IL-6 in vitro.

Keywords: Epstein-Barr virus; Rta; cell migration; interleukin-6; nasopharyngeal carcinoma.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / virology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Janus Kinases / metabolism*
  • MAP Kinase Signaling System
  • MCF-7 Cells
  • Nasopharyngeal Carcinoma / genetics
  • Nasopharyngeal Carcinoma / metabolism
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Carcinoma / virology
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / virology
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / virology
  • Receptors, Interleukin-6 / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / virology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factor AP-1 / metabolism
  • Transfection
  • Up-Regulation

Substances

  • BRLF1 protein, Human herpesvirus 4
  • IL6 protein, human
  • IL6R protein, human
  • Immediate-Early Proteins
  • Interleukin-6
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Transcription Factor AP-1
  • Janus Kinases