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Article: Epstein-Barr Virus miRNA BART2-5p promotes metastasis of nasopharyngeal carcinoma by suppressing RND3

TitleEpstein-Barr Virus miRNA BART2-5p promotes metastasis of nasopharyngeal carcinoma by suppressing RND3
Authors
Issue Date2020
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2020, v. 80 n. 10, p. 1957-1969 How to Cite?
AbstractNasopharyngeal carcinoma is an Epstein–Barr virus (EBV)-related malignancy. Recently, we found that the EBV-encoded miRNA BART2-5p was increased in the serum of patients with preclinical nasopharyngeal carcinoma and that the copy number positively correlated with disease progression. In this study, we established its role in nasopharyngeal carcinoma progression and explored underlying mechanisms and clinical significance. BART2-5p was an independent unfavorable prognostic factor for progression-free survival and its circulating abundance positively associated with distant metastasis. Ectopic expression of BART2-5p promoted migration and invasion of EBV-negative nasopharyngeal carcinoma cells, whereas genetic downregulation of BART2-5p in EBV-positive nasopharyngeal carcinoma cells decreased aggressiveness. Mechanistically, BART2-5p targeted RND3, a negative regulator of Rho signaling. Downregulation of RND3 phenocopied the effect of BART2-5p and reconstitution of RND3 rescued the phenotype. By suppressing RND3, BART2-5p activated Rho signaling to enhance cell motility. These findings suggest a novel role for EBV miRNA BART2-5p in promoting nasopharyngeal carcinoma metastasis and its potential value as a prognostic indicator or therapeutic target. Significance: This study shows that EBV-encoded BART2-5p miRNA suppresses expression of the RND3 Rho family GTPase, consequently promoting ROCK signaling, cell motility, and metastatic behavior of NPC cells.
Persistent Identifierhttp://hdl.handle.net/10722/284519
ISSN
2019 Impact Factor: 9.727
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorJIANG, C-
dc.contributor.authorLi, L-
dc.contributor.authorXiang, YQ-
dc.contributor.authorLung, ML-
dc.contributor.authorZeng, T-
dc.contributor.authorLu, J-
dc.contributor.authorTsao, SW-
dc.contributor.authorZeng, MS-
dc.contributor.authorYun, JP-
dc.contributor.authorKwong, DLW-
dc.contributor.authorGuan, XY-
dc.date.accessioned2020-08-07T08:58:48Z-
dc.date.available2020-08-07T08:58:48Z-
dc.date.issued2020-
dc.identifier.citationCancer Research, 2020, v. 80 n. 10, p. 1957-1969-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/284519-
dc.description.abstractNasopharyngeal carcinoma is an Epstein–Barr virus (EBV)-related malignancy. Recently, we found that the EBV-encoded miRNA BART2-5p was increased in the serum of patients with preclinical nasopharyngeal carcinoma and that the copy number positively correlated with disease progression. In this study, we established its role in nasopharyngeal carcinoma progression and explored underlying mechanisms and clinical significance. BART2-5p was an independent unfavorable prognostic factor for progression-free survival and its circulating abundance positively associated with distant metastasis. Ectopic expression of BART2-5p promoted migration and invasion of EBV-negative nasopharyngeal carcinoma cells, whereas genetic downregulation of BART2-5p in EBV-positive nasopharyngeal carcinoma cells decreased aggressiveness. Mechanistically, BART2-5p targeted RND3, a negative regulator of Rho signaling. Downregulation of RND3 phenocopied the effect of BART2-5p and reconstitution of RND3 rescued the phenotype. By suppressing RND3, BART2-5p activated Rho signaling to enhance cell motility. These findings suggest a novel role for EBV miRNA BART2-5p in promoting nasopharyngeal carcinoma metastasis and its potential value as a prognostic indicator or therapeutic target. Significance: This study shows that EBV-encoded BART2-5p miRNA suppresses expression of the RND3 Rho family GTPase, consequently promoting ROCK signaling, cell motility, and metastatic behavior of NPC cells.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/-
dc.relation.ispartofCancer Research-
dc.titleEpstein-Barr Virus miRNA BART2-5p promotes metastasis of nasopharyngeal carcinoma by suppressing RND3-
dc.typeArticle-
dc.identifier.emailLi, L: lilei728@hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.emailTsao, SW: gswtsao@hku.hk-
dc.identifier.emailKwong, DLW: dlwkwong@hku.hk-
dc.identifier.emailGuan, XY: xyguan@hku.hk-
dc.identifier.authorityLung, ML=rp00300-
dc.identifier.authorityTsao, SW=rp00399-
dc.identifier.authorityKwong, DLW=rp00414-
dc.identifier.authorityGuan, XY=rp00454-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-19-0334-
dc.identifier.pmid32060148-
dc.identifier.scopuseid_2-s2.0-85084924903-
dc.identifier.hkuros312302-
dc.identifier.volume80-
dc.identifier.issue10-
dc.identifier.spage1957-
dc.identifier.epage1969-
dc.publisher.placeUnited States-

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