PLoS Pathogens | |
microRNA dependent and independent deregulation of long non-coding RNAs by an oncogenic herpesvirus | |
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
【 预 览 】
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