2018 GRC NPC
“The Key Cellular Factors in EBV Infection of Epithelial Cells”
- 4912 new cases NPC in 2016
- Bmi-1 induce immortalization of NOC cells
- NPEC1-BMI-1 And NPEC2-BMI-1. Has 10 fold higher efficiency for EBV infection (cell free)
- NMHC-IIA is a poteintial key factor in EBV infection
- NMHC-IIA interacted with gHgL and co-local
- Membrane redistribution f NMHC-IIA which localized with gHgL
- EGF unregulated 5 membrane proteins. (AREG/NT5E, EPHA2, F3, EGFL5, DCBCL2)
- KO down of EPHA2 markedly decreased EBV infection
- gH/gL and gB interact with EPHA2
- NRP1 — gB CendR domain
- NRP1 is a receptor of HTLV
- EBV entered epithelial cells via lipid raft
- EBV internalizes into eputhelial cells in the presence of NRP1 and EphA1
- EBV fuses with endosomatic membrane by binding to EphA2
- Genetic susceptibility of NPC patients
- Genetic variation of EBV strains (full-length sequences of EBV
- Epithelial cell receptors for EBV infection
- Highly susceptible NPCx model
- Cellular factors (The mechanism of EBV infection and transformation in nasopharyngeal carcinoma)
2016 GRC NPC
Mu-Sheng Zeng (Sun Yat-Sen University Cancer Center, China)”NPC, an Epithelial Cancer: Immortalization and Tumorigenesis” 曾木聖
- NMHC-IIA and NRP1 mediate EBV infection by interaction with gHgL and GB，respectively
- NRP1 mediated EGFR signaling is involved in EBV infection
- NP69 + Bmi1 + CCND1 enhances EBV akata EGFP infection to 30%
- Sphere like
- FGFR3-TACC3 (low prevalence in NPC after big-screening)
- ncRNA: RBM24 suppresses CNE2 growth
- MALAT1, miR-25 inhibits MALAT1 expression
- 中山大學Nature子刊揭示病毒致癌新機制 (http://goo.gl/dUieQt)
- Cell子刊：首張致癌EB病毒註釋圖譜 (http://goo.gl/3YsJIs)
From Ming-Han
- LMP2A cause EMT?
- receptor of epithelial cells?
- How EBV infects epithelial cells? hints (1) very low infectivity; (2) usually clonal EBV. (Dougles Hanahan Cell 2011)
Establish immortalised NPECs
- SV40LT
- HPV E6 E7
- Bim-1 (GOOD!) and also highly expressed in bad NPC cases.
How?
- Overexpress Bmi1 immortalised NP cells by reduce p16;
- over express hTERT and stemness pathway.
Now in their lab:
- Bmi1 + hTert or Bmi1 + p16ko: can easily immortalise NP cells and after EBV infection EBV can easily keep inside the cells and keep in latency II.
- Whether EBV infection cause transform and tumorigenesis?
- -in cell infection model (2015)?
- -gp110->CRGDK/R->Neuropilin-1 (NRP-1+gb) increase of NP cells (2015 nature communications)
- -infection of EBV mainly mediated by macropinocytosis; together with EBV bound to NRP-1
Question:
EBV gene expression in NPC by pair-ended transcriptomes
(1) some type III latency may be express in primary NPC tissues and C666 cell line (Fu LJ, teal Front med 2016)
How about cellular gene? any fusion genes in NPC? since it will be good target for drugs.
FGFR3-TACC3 fusion gene: 5% of NPC. (SF: 這個沒搞頭)
RBM24 and NPC: miR25 is down in NPC; over expression of miR25 Block NPC grow and invasion
Q: target of miR25?
@@MALAT1: highly possible target.
model: RBM24hi-> more mir@5-> block MALAT1-> no tumor or vice versa.
Conclusion:
- 1 Bmi1, htert and kd of p16 important of NPEC
- 2 Bmi-1 and cyclinD1 support EBV latent infection in NPECs.
- 3 Sphere-like culture of Bmi-1 immortalised cells support EBV infection
- 4 NHMC-IIA and NRP-1 mediate EBV infection. Importantly; these proteins expressed at low level of normal NPECs but highly in NPCs. http://www.ncbi.nlm.nih.gov/nuccore/323276615
In August EBV Meeting Session 11: EBV and Autoimmunity
Cellular Factors in Epstein-Barr Virus Infection of Nasopharyngeal Epithelial Cells
Mu-Sheng Zeng, Sun Yat-Sen University Cancer Center, Guangzhou, China