Oncotarget

Research Papers:

Viral oncomiR spreading between B and T cells is employed by Kaposi's sarcoma herpesvirus to induce non-cell-autonomous target gene regulation

Nir Rainy _, Morad Zayoud, Yoel Kloog, Oded Rechavi and Itamar Goldstein

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Oncotarget. 2016; 7:41870-41884. https://doi.org/10.18632/oncotarget.9627

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Abstract

Nir Rainy1,2,3, Morad Zayoud1,2, Yoel Kloog3, Oded Rechavi3, Itamar Goldstein1,2

1Sheba Cancer Research Center, Chaim Sheba Academic Medical Center, Tel Hashomer, Ramat Gan 5262100, Israel

2Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel

3Department of Neurobiology, The George S. Wise Faculty of Life Sciences & Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv 6997801, Israel

Correspondence to:

Itamar Goldstein, email: Itamar.Goldstein@sheba.health.gov.il

Keywords: microRNAs, herpesviruses, lymphoma, oncomiRs, viral carcinogenesis

Received: November 08, 2015     Accepted: May 08, 2016     Published: May 26, 2016

ABSTRACT

The two human lymphotrophic γ-herpesviruses, Kaposi's sarcoma herpesvirus (KSHV) and Epstein-Barr virus (EBV), are a recognized cause of human cancer, encoding multiple miRs that are major players in carcinogenesis. Previously, we discovered that EBV-encoded miRs transfer between infected B and T lymphocytes. To further explore the biological significance of the spreading of γ-herpesvirus-encoded miRs on carcinogenesis, we focused on KSHV-miR-K12-11 (miR-K12-11) that is unique in having an identical seed sequence with the oncomiR hsa-miR-155, implicated in B cell lymphomas development. Here, we show for the first time that miR-K12-11 transfers in vitro from KSHV-infected BCBL-1 and BC-1 lymphoma lines to T cells. The transferred miR-K12-11 is active in the adopting T cells and binds its canonical target, the 3’-UTR of BACH1. Importantly, we show that the transfer of miR-K12-11 from BCBL-1 to Jurkat cells correlates with inhibition of the innate type-I interferons response to viral dsRNAs downstream of IKKε, a validated miR-K12-11 target. Finally, we show that miR-K12-11 spreading is not reduced by blocking the classical ceramide-dependent exosome secretion pathway. In summary, we report for the first time that intercellular viral oncomiR spreading is an additional mechanism employed by KSHV to inhibit host anti-viral immunity and consequently promote oncogenesis.


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