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Marek's disease virus-encoded analog of microRNA-155 activates the oncogene c-Myc by targeting LTBP1 and suppressing the TGF-β signaling pathway.

Abstract：

:Marek's disease virus (MDV) is a representative alpha herpes virus able to induce rapid-onset T-cell lymphoma in its natural host and regarded as an ideal model for the study of virus-induced tumorigenesis. Recent studies have shown that the mdv1-miR-M4-5p, a viral analog of cellular miR-155, is critical for MDV׳s oncogenicity. However, the precise mechanism whereby it was involved in MD lymphomagenesis remained unknown. We have presently identified the host mRNA targets of mdv1-miR-M4-5 and identified the latent TGF-β binding protein 1 (LTBP1) as a critical target for it. We found that during MDV infection, down-regulation of LTBP1 expression by mdv1-miR-M4-5p led to a significant decrease of the secretion and activation of TGF-β1, with suppression of TGF-β signaling and a significant activation of expression of c-Myc, a well-known oncogene which is critical for virus-induced tumorigenesis. Our findings reveal a novel and important mechanism of how mdv1-miR-M4-5p potentially contributes to MDV-induced tumorigenesis.

journal_name

Virology

journal_title

Virology

authors

Chi JQ,Teng M,Yu ZH,Xu H,Su JW,Zhao P,Xing GX,Liang HD,Deng RG,Qu LH,Zhang GP,Luo J

doi

10.1016/j.virol.2014.11.027

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

72-84

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(14)00535-2

journal_volume

476

pub_type

杂志文章

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