Functional characterization of Epstein-Barr virus long non-coding RNAs (lnc-BARTs) in nasopharyngeal carcinoma
Grant Data
Project Title
Functional characterization of Epstein-Barr virus long non-coding RNAs (lnc-BARTs) in nasopharyngeal carcinoma
Principal Investigator
Professor Chen, Honglin
(Principal Investigator (PI))
Co-Investigator(s)
Dr Dai Wei
(Co-Investigator)
Duration
36
Start Date
2019-01-01
Completion Date
2021-12-31
Amount
972000
Conference Title
Functional characterization of Epstein-Barr virus long non-coding RNAs (lnc-BARTs) in nasopharyngeal carcinoma
Presentation Title
Keywords
Aiolos, Epstein-Barr Virus, KDM1B, lncRNA, Nasopharyngeal carcinoma
Discipline
Gene Regulation,Cancer
Panel
Biology and Medicine (M)
HKU Project Code
17119618
Grant Type
General Research Fund (GRF)
Funding Year
2018
Status
Completed
Objectives
1 To analyze the effect of lnc-BART RNAs on methylation of host and viral genes in NPC cells. EBV infection is known to lead to global methylation of host genes in associated tumors, but details of the mechanism are unclear. Our pilot study found that some genes which are regulated by methylation in other cancers are also affected by lnc-BART RNAs in EBV infected NPC cells. 2 To study the epigenetic effects, including histone methylation/demethylation, caused by lnc-BART RNAs through induction of KDM1B expression in NPC cells. Genomic imprinting and promoter histone demethylation are important epigenetic processes for regulation of gene expression. We postulate that lnc-BARTs are involved in this process; this hypothesis is supported by our preliminary observation that KDM1B, which is required for genomic imprinting and promoter histone demethylation, is induced by BART lncRNA in EBV infected epithelial cells. 3 To characterize the role of Aiolos expression in NPC cells. Our pilot study found that lnc-BARTs significantly upregulate IKZF3 (Aiolos) in NPC cells. Expression of Aiolos is normally restricted to lymphoid cells, being silenced in epithelial cells through regulation of DNA methylation. Aberrant expression of Aiolos in lung cancer cells is associated with metastasis. It is likely that induction of Aiolos expression by lnc-BART is associated with EBV oncogenesis in NPC. 4 To characterize the molecular basis of lnc-BART RNA regulation of host gene expression in EBV infected epithelial cells. Our pilot study showed that lnc-BART RNAs form nuclear speckles and co-localize with CBP/p300 in the nucleus. This study will analyze in detail the mechanism of lnc-BART RNA action in EBV infected NPC cells.