國家衛生研究院 NHRI:Item 3990099045/13174

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/13174

Title:	Epstein-Barr virus latent membrane protein-1 upregulates autophagy and promotes viability in Hodgkin lymphoma: Implications for targeted therapy
Authors:	Lin, HC;Chang, Y;Chen, RY;Hung, LY;Chen, PC;Chen, YP;Medeiros, LJ;Chiang, PM;Chang, KC
Contributors:	National Institute of Infectious Diseases and Vaccinology
Abstract:	Hodgkin lymphoma (HL) is composed of neoplastic Hodgkin and Reed-Sternberg in an inflammatory background. The neoplastic cells are derived from germinal center B cells that, in most cases, are infected by Epstein-Barr virus (EBV) which may play a role in tumorigenesis. Given that EBV-latent membrane protein 1 (LMP1) regulates autophagy in B cells, we explored the role of autophagy mediated by EBV or LMP1 in HL. We found that EBV-LMP1 transfection in HL cells induced a modest increase in autophagy signals, attenuated starvation-induced autophagic stress, and alleviated autophagy inhibition- or doxorubicin-induced cell death. LMP1 knock-down lead to decreased autophagy LC3 signals. A xenograft mouse model further showed that EBV infection significantly increased expression of the autophagy marker LC3 in HL cells. Clinically, LC3 was expressed in 15% (19/127) of HL samples, but was absent in all cases of nodular lymphocyte-predominant and lymphocyte-rich classic HL cases. Although expression of LC3 was not correlated with EBV status or clinical outcome, autophagic blockade effectively eradicated LMP1-positive HL xenografts with better efficacy than LMP1-negative HL xenografts. Collectively, these results suggest that EBV-LMP1 enhances autophagy and promotes viability of HL cells. Autophagic inhibition may be a potential therapeutic strategy for treating patients with HL, especially EBV-positive cases.
Date:	2021-05
Relation:	Cancer Science. 2021 Apr;112(4):1589-1602.
Link to:	http://dx.doi.org/10.1111/cas.14833
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1347-9032&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000618194600001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85101460455
Appears in Collections:	[Yao Chang] Periodical Articles

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