Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6 promotes cell proliferation and migration by upregulating DNMT1 via STAT3 activation

PLoS One. 2014 Mar 27;9(3):e93478. doi: 10.1371/journal.pone.0093478. eCollection 2014.


Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with Kaposi's sarcoma (KS), the most common AIDS-related malignancy. KSHV vIL-6 promotes KS development, but the exact mechanisms remain unclear. Here, we reported that KSHV vIL-6 enhanced the expression of DNA methyltransferase 1 (DNMT1) in endothelial cells,increased the global genomic DNA methylation, and promoted cell proliferation and migration. And this effect could be blocked by the DNA methyltransferase inhibitor, 5-azadeoxycytidine. We also showed that vIL-6 induced up-regulation of DNMT1 was dependent on STAT3 activation. Therefore, the present study suggests that vIL-6 plays a role in KS tumorigenesis partly by activating DNMT1 and inducing aberrant DNA methylation, and it might be a potential target for KS therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation / drug effects
  • Decitabine
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / virology*
  • Epigenesis, Genetic*
  • Herpesvirus 8, Human / genetics*
  • Herpesvirus 8, Human / metabolism
  • Host-Pathogen Interactions
  • Humans
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism
  • STAT3 Transcription Factor / genetics*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism


  • Antimetabolites, Antineoplastic
  • Interleukin-6
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Viral Proteins
  • interleukin-6, RRV-HHV-8
  • Decitabine
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNMT1 protein, human
  • Azacitidine

Grants and funding

This study was supported by National Natural Science Foundation of China (No. 30901262, 81371894), Key Laboratory for Laboratory Medicine of Jiangsu Province of China (No. XK201114), Medical Science and Technology Development Foundation, Nanjing Department of Health (No. QYK11143), A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.