PMID- 32211095
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200328
IS  - 1936-2625 (Electronic)
IS  - 1936-2625 (Linking)
VI  - 13
IP  - 2
DP  - 2020
TI  - Toll-like receptor 3 (TLR3) functions as a pivotal target in latent membrane 
      protein 1 (LMP1)-mediated nasopharyngeal carcinoma cell proliferation.
PG  - 153-162
AB  - Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) activation of 
      NF-kappaB is pivotal for EBV-infected B lymphocyte survival. Herein, we found that 
      LMP1 markedly rescued the suppressed the proliferation of several nasopharyngeal 
      carcinoma (NPC) cell lines caused by a Toll-like receptor 3 (TLR3) ligand poly 
      (I:C). We profiled the expression alterations of TLR3 and LMP1 within these NPC 
      cell lines in response to poly (I:C) treatment, and found a high correlation 
      between them ws found, suggesting potential involvement of TLR3 in LMP1 
      signaling. Then, cells deficient in TLR3 were used to assess its role in poly 
      (I:C)-induced inhibition of cell proliferation and LMP1-mediated NF-kappaB 
      activation. NF-kappaB p65 activation and the consequent pro-inflammatory responses 
      were unresponsive to poly (I:C) stimulation after TLR3 knockdown (KD), and NOS2 
      and MMP9 were substantially suppressed in CNE1-745, but nearly normal in 
      LMP1-overexpressed CNE1-LMP1-745 cells. This suggests an alternative pathway that 
      LMP1 may depend on, in terms of NOS2 and MMP9 regulation, whereas an unusual 
      TLR3-dependent expression of c-Myc was identified. Consistently, poly 
      (I:C)-induced retarded growth was reversed by TLR3 silencing, which was 
      especially enhanced in LMP1-overexpressed cells. TLR3 is essential for poly 
      (I:C)-incited NPC cell death, and occupies a critical role in LMP1-mediated NF-kappaB 
      activation. Our findings provide new insight into the mechanism underlying 
      LMP1-involved EBV-associated pathogenesis of refractory NPC, thereby potentially 
      improving treatment outcome.
CI  - IJCEP Copyright (c) 2020.
FAU - Zhou, Liang
AU  - Zhou L
AD  - Department of Head Neck Surgery and Operation Suite, The Affiliated Sir Run Run 
      Shaw Hospital, Zhejiang University School of Medicine Zhejiang, P. R. China.
FAU - Hang, Xiaoling
AU  - Hang X
AD  - Department of Head Neck Surgery and Operation Suite, The Affiliated Sir Run Run 
      Shaw Hospital, Zhejiang University School of Medicine Zhejiang, P. R. China.
FAU - Xie, Lei
AU  - Xie L
AD  - Department of Head Neck Surgery and Operation Suite, The Affiliated Sir Run Run 
      Shaw Hospital, Zhejiang University School of Medicine Zhejiang, P. R. China.
LA  - eng
PT  - Journal Article
DEP - 20200201
PL  - United States
TA  - Int J Clin Exp Pathol
JT  - International journal of clinical and experimental pathology
JID - 101480565
PMC - PMC7061799
OTO - NOTNLM
OT  - EB virus
OT  - NF-kappaB
OT  - Nasopharyngeal carcinoma (NPC)
OT  - TLR3
OT  - latent membrane protein 1 (LMP1)
COIS- None.
EDAT- 2020/03/27 06:00
MHDA- 2020/03/27 06:01
PMCR- 2020/02/01
CRDT- 2020/03/27 06:00
PHST- 2019/11/22 00:00 [received]
PHST- 2020/01/23 00:00 [accepted]
PHST- 2020/03/27 06:00 [entrez]
PHST- 2020/03/27 06:00 [pubmed]
PHST- 2020/03/27 06:01 [medline]
PHST- 2020/02/01 00:00 [pmc-release]
PST - epublish
SO  - Int J Clin Exp Pathol. 2020 Feb 1;13(2):153-162. eCollection 2020.