microRNA dependent and independent deregulation of long non-coding RNAs by an oncogenic herpesvirus

PLoS Pathog. 2017 Jul 17;13(7):e1006508. doi: 10.1371/journal.ppat.1006508. eCollection 2017 Jul.

Abstract

Kaposi's sarcoma (KS) is a highly prevalent cancer in AIDS patients, especially in sub-Saharan Africa. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of KS and other cancers like Primary Effusion Lymphoma (PEL). In KS and PEL, all tumors harbor latent KSHV episomes and express latency-associated viral proteins and microRNAs (miRNAs). The exact molecular mechanisms by which latent KSHV drives tumorigenesis are not completely understood. Recent developments have highlighted the importance of aberrant long non-coding RNA (lncRNA) expression in cancer. Deregulation of lncRNAs by miRNAs is a newly described phenomenon. We hypothesized that KSHV-encoded miRNAs deregulate human lncRNAs to drive tumorigenesis. We performed lncRNA expression profiling of endothelial cells infected with wt and miRNA-deleted KSHV and identified 126 lncRNAs as putative viral miRNA targets. Here we show that KSHV deregulates host lncRNAs in both a miRNA-dependent fashion by direct interaction and in a miRNA-independent fashion through latency-associated proteins. Several lncRNAs that were previously implicated in cancer, including MEG3, ANRIL and UCA1, are deregulated by KSHV. Our results also demonstrate that KSHV-mediated UCA1 deregulation contributes to increased proliferation and migration of endothelial cells.

MeSH terms

  • Cell Line
  • Herpesvirus 8, Human / genetics
  • Herpesvirus 8, Human / physiology*
  • Host-Pathogen Interactions
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*
  • Sarcoma, Kaposi / genetics*
  • Sarcoma, Kaposi / metabolism
  • Sarcoma, Kaposi / virology
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • Virus Latency

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Viral
  • Viral Proteins