title: Targeting of DICE1 tumor suppressor by Epstein-Barr virus-encoded miR-BART3* microRNA in nasopharyngeal carcinoma.
abstract: Latent infection with Epstein-Barr virus (EBV) is associated with several types of malignancies including nasopharyngeal carcinoma (NPC), which is particularly more prevalent in Southern China. EBV expresses at least 44 mature microRNAs (miRNAs) to modulate the activity of viral and cellular RNAs, but the targets of these EBV-encoded miRNAs in NPC are not well understood. In this report, we characterized DICE1 tumor suppressor to be a cellular target of EBV miR-BART3* miRNA. miR-BART3* was abundantly expressed in NPC cells. The target site of miR-BART3* located in the 3'-untranslated region of DICE1 transcript was identified and characterized. Enforced expression of miR-BART3* or its precursor pre-miR-BART3 led to down-regulation of endogenous DICE1 expression. Inhibition of endogenous miR-BART3* in NPC cells with anti-miR-BART3* oligonucleotide inhibitor resulted in increased expression of DICE1 protein. On the contrary, expression of miR-BART3* overcame the growth suppressive activity of DICE1 and stimulated cell proliferation. Consistent with its tumor suppressive function, DICE1 was underexpressed in EBV-expressing NPC tumor tissues. Taken together, our findings suggest that EBV encoded miR-BART3* miRNA targets DICE1 tumor suppressor to promote cellular growth and transformation in NPC.
authors.affiliation: Department of Pathology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lei
authors.forename: Kit-San
authors.initials: KS
authors.lastname: Yuen
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
authors.forename: Honglin
authors.initials: H
authors.lastname: Chen
authors.forename: Mengfeng
authors.initials: M
authors.lastname: Li
authors.forename: Kin-Hang
authors.initials: KH
authors.lastname: Kok
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Jin
mesh_terms: D015153:Blotting, Western; D002277:Carcinoma; D002681:China; D015536:Down-Regulation; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D057809:HEK293 Cells; D006367:HeLa Cells; D004854:Herpesvirus 4, Human; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000821:virology*; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C121427:INTS6 protein, human; C581583:MIRN-BART3 microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D025521:Tumor Suppressor Proteins