Oncotarget

Research Papers:

Epstein-Barr virus encoded miR-BART11 promotes inflammation-induced carcinogenesis by targeting FOXP1

Yali Song _, Xiaoling Li, Zhaoyang Zeng, Qiao Li, Zhaojian Gong, Qianjin Liao, Xiayu Li, Pan Chen, Bo Xiang, Wenling Zhang, Fang Xiong, Yanhong Zhou, Ming Zhou, Jian Ma, Yong Li, Xiang Chen, Guiyuan Li and Wei Xiong

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Oncotarget. 2016; 7:36783-36799. https://doi.org/10.18632/oncotarget.9170

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Abstract

Yali Song1,2, Xiaoling Li1,2,3, Zhaoyang Zeng1,2,3, Qiao Li2, Zhaojian Gong2, Qianjin Liao4, Xiayu Li3, Pan Chen4, Bo Xiang1,2,3, Wenling Zhang2, Fang Xiong1, Yanhong Zhou2, Ming Zhou2, Jian Ma2, Yong Li2,5, Xiang Chen1, Guiyuan Li1,2,3, Wei Xiong1,2,3

1The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China

2The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China

3Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

4Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China

5Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA

Correspondence to:

Zhaoyang Zeng, e-mail: [email protected]

Wei Xiong, e-mail: [email protected]

Keywords: nasopharyngeal carcinoma, gastric cancer, Epstein-Barr virus, EBV-miR-BART11, FOXP1

Received: February 09, 2016    Accepted: April 16, 2016    Published: May 4, 2016

ABSTRACT

Epstein-Barr virus (EBV) infection and chronic inflammation are closely associated with the development and progression of nasopharyngeal carcinoma (NPC) and gastric cancer (GC), and the infiltration of inflammatory cells, including tumor-associated macrophages (TAMs), is often observed in these cancers. EBV encodes 44 mature micro RNAs (miRNAs), but the roles of only a few EBV-encoded miRNA targets are known in cancer development, and here, our aim was to elucidate the effects of EBV-miR-BART11 on FOXP1 expression, and potential involvement in inflammation-induced carcinogenesis. We constructed an EBV miRNA-dependent gene regulatory network and predicted that EBV-miR-BART11 is able to target forkhead box P1 (FOXP1), a key molecule involved in monocyte to macrophage differentiation. Here, using luciferase reporter assay, we confirmed that EBV-miR-BART11 directly targets the 3′-untranslated region of FOXP1 gene, inhibits FOXP1 induction of TAM differentiation, and the secretion of inflammatory cytokines into the tumor microenvironment, inducing the proliferation of NPC and GC cells. FOXP1 overexpression hindered monocyte differentiation and inhibited NPC and GC cells growth. Our results demonstrated that EBV-miR-BART11 plays a crucial role in the promotion of inflammation-induced NPC and GC carcinogenesis by inhibiting FOXP1 tumor-suppressive effects. We showed a novel EBV-dependent mechanism that may induce the carcinogenesis of NPC and GC, which may help define new potential biomarkers and targets for NPC and GC diagnosis and treatment.


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