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

PLoS Pathogens

Lauren Appleby Gay¹  Rolf Renne¹  Sunantha Sethuraman¹  Irina Haecker¹  Vaibhav Jain¹ 

[1] Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America

关键词: Long non-coding RNAs;    MicroRNAs;    Kaposi's sarcoma-associated herpesvirus;    Endothelial cells;    Viral persistence;    latency;    Carcinogenesis;    Gene expression;    Microarrays;   

DOI  :  10.1371/journal.ppat.1006508

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY