The interplay between host cell genetics and Epstein-Barr virus(EBV) infection contributes to the development of nasopharyngeal carcinoma(NPC). Understanding the host genetic and epigenetic alterations and the influen...The interplay between host cell genetics and Epstein-Barr virus(EBV) infection contributes to the development of nasopharyngeal carcinoma(NPC). Understanding the host genetic and epigenetic alterations and the influence of EBV on cell signaling and host gene regulation will aid in understanding the molecular pathogenesis of NPC and provide useful biomarkers and targets for diagnosis and therapy. In this review, we provide an update of the oncogenes and tumor suppressor genes associated with NPC, as well as genes associated with NPC risk including those involved in carcinogen detoxification and DNA repair. We also describe the importance of host genetics that govern the human leukocyte antigen(HLA) complex and immune responses, and we describe the impact of EBV infection on host cell signaling changes and epigenetic regulation of gene expression. High-power genomic sequencing approaches are needed to elucidate the genetic basis for inherited susceptibility to NPC and to identify the genes and pathways driving its molecular pathogenesis.展开更多
Dear Editor,Nasopharyngeal carcinoma(NPC)is a common malignancy in East and Southeast Asia,especially in South China.The etiology of NPC has been linked to genetic susceptibility,Epstein-Barr virus(EBV)infection,and e...Dear Editor,Nasopharyngeal carcinoma(NPC)is a common malignancy in East and Southeast Asia,especially in South China.The etiology of NPC has been linked to genetic susceptibility,Epstein-Barr virus(EBV)infection,and environmental factors.Accumulated evidence including multiple genome-wide association studies(GWASs)has revealed robust genetic predisposition of NPC.However,GWAS-identified genetic variants collectively account for only 8.2%of NPC heritability[1].The underlying inherited predisposition is largely undetermined.The strongest genetic signal for NPC consistently hits the human leukocyte antigen(HLA)region on 6p21[2].However,the highly polymorphic nature and complicated long-range linkage disequilibrium(LD)in the HLA region particularly obscure the causal variants driving the association.In addition,most genetic variants located in introns or intergenic regions.The causal genes mediating genetic effects on NPC risk have rarely been ascertained by GWAS alone.展开更多
Nasopharyngeal carcinoma(NPC)is a malignant disease associated with Epstein–Barr virus(EBV)infection.This study aims to examine the effects of EBV infection on the production of proinflammatory cytokines in NPC cells...Nasopharyngeal carcinoma(NPC)is a malignant disease associated with Epstein–Barr virus(EBV)infection.This study aims to examine the effects of EBV infection on the production of proinflammatory cytokines in NPC cells after the Zn-BC-AM photodynamic therapy(PDT)treatment.Cells were treated with the photosensitiser Zn-BC-AM for 24 h before light irradiation.Quantitative ELISA was used to evaluate the production of cytokines.Under the same experimental condition,HK-1-EBV cells produced a higher basal level of IL-1a(1561 pg/ml),IL-1b(16.6 pg/ml)and IL-8(422.9 pg/ml)than the HK-1 cells.At the light dose of 0.25–0.5 J/cm2,Zn-BC-AM PDT-treated HK-1-EBV cells were found to produce a higher level of IL-1a and IL-1b than the HK-1 cells.The production of IL-1b appeared to be mediated via the IL-1b-converting enzyme(ICE)-independent pathway.In contrast,the production of angiogenic IL-8 was downregulated in both HK-1 and HK-1-EBV cells after Zn-BC-AM PDT.Our results suggest that Zn-BC-AM PDT might indirectly reduce tumour growth through the modulation of cytokine production.展开更多
基金supported by the Research Grants Council Area of Excellence grant (AoE/M-06/08)
文摘The interplay between host cell genetics and Epstein-Barr virus(EBV) infection contributes to the development of nasopharyngeal carcinoma(NPC). Understanding the host genetic and epigenetic alterations and the influence of EBV on cell signaling and host gene regulation will aid in understanding the molecular pathogenesis of NPC and provide useful biomarkers and targets for diagnosis and therapy. In this review, we provide an update of the oncogenes and tumor suppressor genes associated with NPC, as well as genes associated with NPC risk including those involved in carcinogen detoxification and DNA repair. We also describe the importance of host genetics that govern the human leukocyte antigen(HLA) complex and immune responses, and we describe the impact of EBV infection on host cell signaling changes and epigenetic regulation of gene expression. High-power genomic sequencing approaches are needed to elucidate the genetic basis for inherited susceptibility to NPC and to identify the genes and pathways driving its molecular pathogenesis.
基金the National Key Research and Development Program of China(2021YFC2500400)the Basic and Applied Basic Research Foundation of Guangdong Province,China(2021B1515420007)+4 种基金Sino-Sweden Joint Research Programme(81861138006)the Science and Technology Planning Project of Guangzhou,China(201804020094)the Special Support Program for High-level Professionals on Scientific and Technological Innovation of Guangdong Province,China(2014TX01R201)National Natural Science Foundation of China(81973131,81903395,81803319,82003520)National Science Fund for Distinguished Young Scholars of China(81325018).
文摘Dear Editor,Nasopharyngeal carcinoma(NPC)is a common malignancy in East and Southeast Asia,especially in South China.The etiology of NPC has been linked to genetic susceptibility,Epstein-Barr virus(EBV)infection,and environmental factors.Accumulated evidence including multiple genome-wide association studies(GWASs)has revealed robust genetic predisposition of NPC.However,GWAS-identified genetic variants collectively account for only 8.2%of NPC heritability[1].The underlying inherited predisposition is largely undetermined.The strongest genetic signal for NPC consistently hits the human leukocyte antigen(HLA)region on 6p21[2].However,the highly polymorphic nature and complicated long-range linkage disequilibrium(LD)in the HLA region particularly obscure the causal variants driving the association.In addition,most genetic variants located in introns or intergenic regions.The causal genes mediating genetic effects on NPC risk have rarely been ascertained by GWAS alone.
基金supported by the Research Grant Council of Hong Kong(HKBU2052/02M and HKBU2458/06M).
文摘Nasopharyngeal carcinoma(NPC)is a malignant disease associated with Epstein–Barr virus(EBV)infection.This study aims to examine the effects of EBV infection on the production of proinflammatory cytokines in NPC cells after the Zn-BC-AM photodynamic therapy(PDT)treatment.Cells were treated with the photosensitiser Zn-BC-AM for 24 h before light irradiation.Quantitative ELISA was used to evaluate the production of cytokines.Under the same experimental condition,HK-1-EBV cells produced a higher basal level of IL-1a(1561 pg/ml),IL-1b(16.6 pg/ml)and IL-8(422.9 pg/ml)than the HK-1 cells.At the light dose of 0.25–0.5 J/cm2,Zn-BC-AM PDT-treated HK-1-EBV cells were found to produce a higher level of IL-1a and IL-1b than the HK-1 cells.The production of IL-1b appeared to be mediated via the IL-1b-converting enzyme(ICE)-independent pathway.In contrast,the production of angiogenic IL-8 was downregulated in both HK-1 and HK-1-EBV cells after Zn-BC-AM PDT.Our results suggest that Zn-BC-AM PDT might indirectly reduce tumour growth through the modulation of cytokine production.