Latent mermbrane protein 1(LMP1)is known as an oncoprotein in nasopharyngeal carcinoma(NPC)cells,which is considered to have a strong association with growth,invasion and metastasis of NPC cells through lipid rafts.Me...Latent mermbrane protein 1(LMP1)is known as an oncoprotein in nasopharyngeal carcinoma(NPC)cells,which is considered to have a strong association with growth,invasion and metastasis of NPC cells through lipid rafts.Met hy-A-cyclodextrin(M3CD)can disrupt lipid rafts through cholesterol depletion.In this study,we revealed that MICD induced apoptosis in two kinds of NPC cells including CNE1 cells,a LMP1 negative nasopharyngeal squamous carcinoma cell line,and CNE1-LMP1 cells,a LMP1-positive nasopharyngeal squamous carcinoma cell line.Furthermore,the impact of MBCD on LMP1 was investigated by fuorescence resonance energy transfer(FRET)method in NPC cells.Synchronized tempo spatial and spectral detection of LMP1/LMP1 interaction were performed using fluorescence microscope and spectrograph.FRET efficiency indicated that LMP1/LMP1 interaction gradully enhanced after M9CD treatment.MTT assays showed that M8CD caused strong cytotoxicity in CNE1 cells,but cauused relatively weaker cytotoxicity in CNE1-LMP1 cells,which indicated that LMP1 may regulate sensitivity of NPC cells to MBCD.Then,detection of cleaved caspase-3 in two kinds of NPC cells indicated that LMP1 may inhibit activation of caspase 3.These results strongly suggested that MBCD can induce apoptosis of NPC cells,but enhancing of LMP1/LMP1 interaction may likely resist apoptosis through inhibiting cleavage of caspase-3.展开更多
Back ground: Non-Hodgkin’s lymphoma (NHL) with its different subtypes is strongly related to Epstein Bar virus (EBV) infection mainly Burkitt’s lymphoma in Africa. Studies proved the role of EBV in tumor-genesis and...Back ground: Non-Hodgkin’s lymphoma (NHL) with its different subtypes is strongly related to Epstein Bar virus (EBV) infection mainly Burkitt’s lymphoma in Africa. Studies proved the role of EBV in tumor-genesis and linked it to prognosis and therapy of patients. Objectives: To determine the frequency of EBV in non-Hodgkin lymphomas using EBV latent membrane protein 1 (EBV-LMP1) immunohistochemical stain. Methods: This cross-sectional study was conducted at radio-isotope centre of Khartoum (2012-2014). A total of 75 cases of non-Hodgkin lymphoma paraffin embedded sections were stained for EBV LMP1 antibody. Data were analyzed by SPSS 16 and statistical cross linking of the results of immune staining with other data was done. Results: Out of 75 patients of non Hodgkin’s lymphoma (74.7%) were males. EBV-LMP1 Immune-staining was positive in (17.3%) with predominance of Burkitt’s lymphoma (33.3%), followed by diffuse large B cell lymphoma (17.9%). Conclusion: Burkitt’s lymphoma expressed the highest percentage of non-Hodgkin’s lymphoma positive cases (46.2%) out of the total (17.3%) positive cases. Different methods need to be used in studying Burkitt’s lymphoma expression of EBV and its effects on the treatment and prognosis of cases.展开更多
[目的]检测EB病毒(EBV)阳性肺癌组织中EBV潜伏感染膜蛋白-1(LMP-1)、p53、Bcl-2及基质金属蛋白酶-9(MMP-9)表达情况,分析它们与肺癌发生发展的关系。[方法]采用原位杂交法检测108例肺癌组织和22例癌旁正常肺组织中EBV编码的小RNA-1(EBV ...[目的]检测EB病毒(EBV)阳性肺癌组织中EBV潜伏感染膜蛋白-1(LMP-1)、p53、Bcl-2及基质金属蛋白酶-9(MMP-9)表达情况,分析它们与肺癌发生发展的关系。[方法]采用原位杂交法检测108例肺癌组织和22例癌旁正常肺组织中EBV编码的小RNA-1(EBV encoded small RNA-1,EBER-1)。免疫组织化学的方法检测EBER-1阳性和阴性肺癌组织中LMP-1、p53、Bcl-2及MMP-9的表达。[结果]108例肺癌组织中EBER-1阳性36例,阳性率33.3%;22例癌旁正常肺组织中EBER-1阳性1例,阳性率4.5%,差异有统计学意义(P<0.01)。EBER-1阳性和阴性的肺癌组织中LMP-1阳性率分别为11.1%和4.2%,差异无统计学意义(P>0.05);在EBER-1阳性肺癌组织中p53、Bcl-2的平均面积(AA)和积分光密度(IOD)均高于阴性组,差异有统计学意义。在EBER-1阳性肺癌组织中MMP-9AA和IOD均高于阴性组,但差异无统计学意义(P>0.05)。[结论]EBV感染可能通过影响LMP-1、Bcl-2、p53和MMP-9在肺癌组织中的表达,进而在肺癌的发生、发展和转移中发挥作用。展开更多
The AKT/mTOR and NF-κB signalings are crucial pathways activated in cancers including nasopharyngeal carcinoma(NPC), which is prevalent in southern China and closely related to Epstein-Barr virus(EBV) infection.How t...The AKT/mTOR and NF-κB signalings are crucial pathways activated in cancers including nasopharyngeal carcinoma(NPC), which is prevalent in southern China and closely related to Epstein-Barr virus(EBV) infection.How these master pathways are persistently activated in EBV-associated NPC remains to be investigated. Here we demonstrated that EBV-encoded latent membrane protein 1(LMP1) promoted cyclophilin A(CYPA) expression through the activation of NF-κB. The depletion of CYPA suppressed cell proliferation and facilitated apoptosis.CYPA was able to bind to AKT1, thus activating AKT/mTOR/NF-κB signaling cascade. Moreover, the use of mTOR inhibitor, rapamycin, subverted the activation of the positive feedback loop, NF-κB/CYPA/AKT/mTOR. It is reasonable that LMP1 expression derived from initial viral infection is enough to assure the constant potentiation of AKT/mTOR and NF-κB signalings. This may partly explain the fact that EBV serves as a tumor-promoting factor with minimal expression of the viral oncoprotein LMP1 in malignancies. Our findings provide new insight into the understanding of causative role of EBV in tumorigenicity during latent infection.展开更多
基金supported by the National Key Basic Research Program of China(No.2015CB352006)the National Natural Science Foundation of China(Nos.61335011,61775037 and 61475036)+2 种基金Program for Changjiang Scholars and Innovative Research Team in University(No.IRT 15R10)Natural Science Foundation of Fujian Province of China(Nos.2019J01270 and 2017J01844)the High level Joint Research and Construction Program of Fujian Provincial Hospital,and Special Funds of the Central Government Guiding Local Science and Technology Development(2017L3009),China.
文摘Latent mermbrane protein 1(LMP1)is known as an oncoprotein in nasopharyngeal carcinoma(NPC)cells,which is considered to have a strong association with growth,invasion and metastasis of NPC cells through lipid rafts.Met hy-A-cyclodextrin(M3CD)can disrupt lipid rafts through cholesterol depletion.In this study,we revealed that MICD induced apoptosis in two kinds of NPC cells including CNE1 cells,a LMP1 negative nasopharyngeal squamous carcinoma cell line,and CNE1-LMP1 cells,a LMP1-positive nasopharyngeal squamous carcinoma cell line.Furthermore,the impact of MBCD on LMP1 was investigated by fuorescence resonance energy transfer(FRET)method in NPC cells.Synchronized tempo spatial and spectral detection of LMP1/LMP1 interaction were performed using fluorescence microscope and spectrograph.FRET efficiency indicated that LMP1/LMP1 interaction gradully enhanced after M9CD treatment.MTT assays showed that M8CD caused strong cytotoxicity in CNE1 cells,but cauused relatively weaker cytotoxicity in CNE1-LMP1 cells,which indicated that LMP1 may regulate sensitivity of NPC cells to MBCD.Then,detection of cleaved caspase-3 in two kinds of NPC cells indicated that LMP1 may inhibit activation of caspase 3.These results strongly suggested that MBCD can induce apoptosis of NPC cells,but enhancing of LMP1/LMP1 interaction may likely resist apoptosis through inhibiting cleavage of caspase-3.
文摘Back ground: Non-Hodgkin’s lymphoma (NHL) with its different subtypes is strongly related to Epstein Bar virus (EBV) infection mainly Burkitt’s lymphoma in Africa. Studies proved the role of EBV in tumor-genesis and linked it to prognosis and therapy of patients. Objectives: To determine the frequency of EBV in non-Hodgkin lymphomas using EBV latent membrane protein 1 (EBV-LMP1) immunohistochemical stain. Methods: This cross-sectional study was conducted at radio-isotope centre of Khartoum (2012-2014). A total of 75 cases of non-Hodgkin lymphoma paraffin embedded sections were stained for EBV LMP1 antibody. Data were analyzed by SPSS 16 and statistical cross linking of the results of immune staining with other data was done. Results: Out of 75 patients of non Hodgkin’s lymphoma (74.7%) were males. EBV-LMP1 Immune-staining was positive in (17.3%) with predominance of Burkitt’s lymphoma (33.3%), followed by diffuse large B cell lymphoma (17.9%). Conclusion: Burkitt’s lymphoma expressed the highest percentage of non-Hodgkin’s lymphoma positive cases (46.2%) out of the total (17.3%) positive cases. Different methods need to be used in studying Burkitt’s lymphoma expression of EBV and its effects on the treatment and prognosis of cases.
文摘[目的]检测EB病毒(EBV)阳性肺癌组织中EBV潜伏感染膜蛋白-1(LMP-1)、p53、Bcl-2及基质金属蛋白酶-9(MMP-9)表达情况,分析它们与肺癌发生发展的关系。[方法]采用原位杂交法检测108例肺癌组织和22例癌旁正常肺组织中EBV编码的小RNA-1(EBV encoded small RNA-1,EBER-1)。免疫组织化学的方法检测EBER-1阳性和阴性肺癌组织中LMP-1、p53、Bcl-2及MMP-9的表达。[结果]108例肺癌组织中EBER-1阳性36例,阳性率33.3%;22例癌旁正常肺组织中EBER-1阳性1例,阳性率4.5%,差异有统计学意义(P<0.01)。EBER-1阳性和阴性的肺癌组织中LMP-1阳性率分别为11.1%和4.2%,差异无统计学意义(P>0.05);在EBER-1阳性肺癌组织中p53、Bcl-2的平均面积(AA)和积分光密度(IOD)均高于阴性组,差异有统计学意义。在EBER-1阳性肺癌组织中MMP-9AA和IOD均高于阴性组,但差异无统计学意义(P>0.05)。[结论]EBV感染可能通过影响LMP-1、Bcl-2、p53和MMP-9在肺癌组织中的表达,进而在肺癌的发生、发展和转移中发挥作用。
基金supported by the Natural Science Foundations of China(81974427)Graduate Research and Innovation Projects of Central South University(2021zzts0931)
文摘The AKT/mTOR and NF-κB signalings are crucial pathways activated in cancers including nasopharyngeal carcinoma(NPC), which is prevalent in southern China and closely related to Epstein-Barr virus(EBV) infection.How these master pathways are persistently activated in EBV-associated NPC remains to be investigated. Here we demonstrated that EBV-encoded latent membrane protein 1(LMP1) promoted cyclophilin A(CYPA) expression through the activation of NF-κB. The depletion of CYPA suppressed cell proliferation and facilitated apoptosis.CYPA was able to bind to AKT1, thus activating AKT/mTOR/NF-κB signaling cascade. Moreover, the use of mTOR inhibitor, rapamycin, subverted the activation of the positive feedback loop, NF-κB/CYPA/AKT/mTOR. It is reasonable that LMP1 expression derived from initial viral infection is enough to assure the constant potentiation of AKT/mTOR and NF-κB signalings. This may partly explain the fact that EBV serves as a tumor-promoting factor with minimal expression of the viral oncoprotein LMP1 in malignancies. Our findings provide new insight into the understanding of causative role of EBV in tumorigenicity during latent infection.
