title: Epstein-Barr virus encoded miR-BART11 promotes inflammation-induced carcinogenesis by targeting FOXP1.
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.
authors.affiliation: The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.|The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Song
authors.affiliation: The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.|The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.affiliation: The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.|The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Li
authors.affiliation: The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Zhaojian
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Hunan 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.
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Liao
authors.affiliation: Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiayu
authors.initials: X
authors.lastname: Li
authors.affiliation: Hunan 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.
authors.forename: Pan
authors.initials: P
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.|The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiang
authors.affiliation: The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Wenling
authors.initials: W
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xiong
authors.affiliation: The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.|Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.|The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
authors.affiliation: The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.|The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000821:virology; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000150:complications; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000821:virology; D034622:RNA Interference; D012367:RNA, Viral / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics* / Q000821:virology
chemical_list: D020413:3' Untranslated Regions; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D035683:MicroRNAs; C000625713:Mir-BART11, Epstein-Barr virus; D016328:NF-kappa B; D012367:RNA, Viral; D012097:Repressor Proteins
keywords: EBV-miR-BART11; Epstein-Barr virus; FOXP1; gastric cancer; nasopharyngeal carcinoma