Document Detail


A Kaposi's sarcoma-associated herpesvirus microRNA and its variants target the transforming growth factor β pathway to promote cell survival.
MedLine Citation:
PMID:  22915806     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transforming growth factor β (TGF-β) signaling regulates cell growth and survival. Dysregulation of the TGF-β pathway is common in viral infection and cancer. Latent infection by Kaposi's sarcoma-associated herpesvirus (KSHV) is required for the development of several AIDS-related malignancies, including Kaposi's sarcoma and primary effusion lymphoma (PEL). KSHV encodes more than two dozen microRNAs (miRs) derived from 12 pre-miRs with largely unknown functions. In this study, we show that miR variants processed from pre-miR-K10 are expressed in KSHV-infected PEL cells and endothelial cells, while cellular miR-142-3p and its variant miR-142-3p_-1_5, which share the same seed sequence with miR-K10a_ +1_5, are expressed only in PEL cells and not in uninfected and KSHV-infected TIME cells. KSHV miR-K10 variants inhibit TGF-β signaling by targeting TGF-β type II receptor (TβRII). Computational and reporter mutagenesis analyses identified three functional target sites in the TβRII 3' untranslated region (3'UTR). Expression of miR-K10 variants is sufficient to inhibit TGF-β-induced cell apoptosis. A suppressor of the miRs sensitizes latent KSHV-infected PEL cells to TGF-β and induces apoptosis. These results indicate that miR-K10 variants manipulate the TGF-β pathway to confer cells with resistance to the growth-inhibitory effect of TGF-β. Thus, KSHV miRs might target the tumor-suppressive TGF-β pathway to promote viral latency and contribute to malignant cellular transformation.
Authors:
Xiufen Lei; Ying Zhu; Tiffany Jones; Zhiqiang Bai; Yufei Huang; Shou-Jiang Gao
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-22
Journal Detail:
Title:  Journal of virology     Volume:  86     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-08     Completed Date:  2013-01-07     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11698-711     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Apoptosis
Cell Line
Cell Survival
Herpesvirus 8, Human / immunology*,  pathogenicity*
Humans
Immune Evasion*
MicroRNAs / genetics,  metabolism*
RNA, Viral / genetics,  metabolism*
Transforming Growth Factor beta / antagonists & inhibitors*
Grant Support
ID/Acronym/Agency:
CA096512/CA/NCI NIH HHS; CA119889/CA/NCI NIH HHS; CA124332/CA/NCI NIH HHS; R01 CA096512/CA/NCI NIH HHS; R01 CA106159/CA/NCI NIH HHS; R01 CA124332/CA/NCI NIH HHS; R01 CA132637/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/MicroRNAs; 0/RNA, Viral; 0/Transforming Growth Factor beta
Comments/Corrections

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