Activation of MEK1/2/Nrf-2 Signaling Pathway by Epstein-Barr Virus-Latent Membrane Protein 1 Enhances Autophagy and Cisplatin Resistance in T-Cell Lymphoma
Epstein-Barr virus-latent membrane protein 1 (EBV-LMP1) was associated with lymphoma, but its specific mechanism is still controversial. The study is aimed at studying the regulation of lymphoma resistance by EBV-LMP1 through the MEK1/2/Nrf-2 signaling pathway. First, LMP1 was knocked down in EBV-po...
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| Format: | Article |
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Wiley
2021-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2021/6668947 |
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| author | Xintao Jia Qiuyu He Mei Zeng Yuhua Chen Yan Liu |
| author_facet | Xintao Jia Qiuyu He Mei Zeng Yuhua Chen Yan Liu |
| author_sort | Xintao Jia |
| collection | DOAJ |
| description | Epstein-Barr virus-latent membrane protein 1 (EBV-LMP1) was associated with lymphoma, but its specific mechanism is still controversial. The study is aimed at studying the regulation of lymphoma resistance by EBV-LMP1 through the MEK1/2/Nrf-2 signaling pathway. First, LMP1 was knocked down in EBV-positive SNK-6 cells and overexpressed in EBV-negative KHYG-1 cells. First, we found that overexpression of LMP1 significantly promoted the resistance of KHYG-1 cells to cisplatin (DDP), which was related to increased autophagy in the cells. In contrast, knockdown of LMP1 expression in SNK-6 cells promoted cellular sensitivity to DDP and reduced the autophagy of cells after DDP treatment. Moreover, specific inhibition of autophagy in KHYG-1 cells significantly attenuated the resistance to DDP caused by overexpression of LMP1, but treatment with rapamycin in SNK-6 cells significantly promoted the autophagy in the cells. Subsequently, overexpression of LMP1 promoted the activation of the MEK1/2-Nrf2 pathway in KYHG-1 cells, whereas knockdown of LMP1 in SNK-6 cells inhibited the activation of the MEK1/2-Nrf2 pathway. Inhibition of MEK1/2/Nrf-2 blocked the promoting effects of LMP1 on lymphoma cell resistance. In conclusion, EBV-LMP1 promotes cell autophagy after DDP treatment by activating the MEK1/2/Nrf-2 signaling pathway in lymphoma cells, thus, enhancing the resistance of lymphoma cells to DDP. |
| format | Article |
| id | doaj-art-62affd38020044668fc1e9fb6e27bf7b |
| institution | Kabale University |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
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| series | Analytical Cellular Pathology |
| spelling | doaj-art-62affd38020044668fc1e9fb6e27bf7b2025-02-03T01:08:52ZengWileyAnalytical Cellular Pathology2210-71772210-71852021-01-01202110.1155/2021/66689476668947Activation of MEK1/2/Nrf-2 Signaling Pathway by Epstein-Barr Virus-Latent Membrane Protein 1 Enhances Autophagy and Cisplatin Resistance in T-Cell LymphomaXintao Jia0Qiuyu He1Mei Zeng2Yuhua Chen3Yan Liu4Department of Pathology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Sciences, Xiangyang, 441021 Hubei, ChinaDepartment of Pathology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Sciences, Xiangyang, 441021 Hubei, ChinaDepartment of Pathology Teaching and Research Section, Xiangyang Polytechnic, Xiangyang, 441050 Hubei, ChinaDepartment of Pathology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Sciences, Xiangyang, 441021 Hubei, ChinaDepartment of Pathology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Sciences, Xiangyang, 441021 Hubei, ChinaEpstein-Barr virus-latent membrane protein 1 (EBV-LMP1) was associated with lymphoma, but its specific mechanism is still controversial. The study is aimed at studying the regulation of lymphoma resistance by EBV-LMP1 through the MEK1/2/Nrf-2 signaling pathway. First, LMP1 was knocked down in EBV-positive SNK-6 cells and overexpressed in EBV-negative KHYG-1 cells. First, we found that overexpression of LMP1 significantly promoted the resistance of KHYG-1 cells to cisplatin (DDP), which was related to increased autophagy in the cells. In contrast, knockdown of LMP1 expression in SNK-6 cells promoted cellular sensitivity to DDP and reduced the autophagy of cells after DDP treatment. Moreover, specific inhibition of autophagy in KHYG-1 cells significantly attenuated the resistance to DDP caused by overexpression of LMP1, but treatment with rapamycin in SNK-6 cells significantly promoted the autophagy in the cells. Subsequently, overexpression of LMP1 promoted the activation of the MEK1/2-Nrf2 pathway in KYHG-1 cells, whereas knockdown of LMP1 in SNK-6 cells inhibited the activation of the MEK1/2-Nrf2 pathway. Inhibition of MEK1/2/Nrf-2 blocked the promoting effects of LMP1 on lymphoma cell resistance. In conclusion, EBV-LMP1 promotes cell autophagy after DDP treatment by activating the MEK1/2/Nrf-2 signaling pathway in lymphoma cells, thus, enhancing the resistance of lymphoma cells to DDP.http://dx.doi.org/10.1155/2021/6668947 |
| spellingShingle | Xintao Jia Qiuyu He Mei Zeng Yuhua Chen Yan Liu Activation of MEK1/2/Nrf-2 Signaling Pathway by Epstein-Barr Virus-Latent Membrane Protein 1 Enhances Autophagy and Cisplatin Resistance in T-Cell Lymphoma Analytical Cellular Pathology |
| title | Activation of MEK1/2/Nrf-2 Signaling Pathway by Epstein-Barr Virus-Latent Membrane Protein 1 Enhances Autophagy and Cisplatin Resistance in T-Cell Lymphoma |
| title_full | Activation of MEK1/2/Nrf-2 Signaling Pathway by Epstein-Barr Virus-Latent Membrane Protein 1 Enhances Autophagy and Cisplatin Resistance in T-Cell Lymphoma |
| title_fullStr | Activation of MEK1/2/Nrf-2 Signaling Pathway by Epstein-Barr Virus-Latent Membrane Protein 1 Enhances Autophagy and Cisplatin Resistance in T-Cell Lymphoma |
| title_full_unstemmed | Activation of MEK1/2/Nrf-2 Signaling Pathway by Epstein-Barr Virus-Latent Membrane Protein 1 Enhances Autophagy and Cisplatin Resistance in T-Cell Lymphoma |
| title_short | Activation of MEK1/2/Nrf-2 Signaling Pathway by Epstein-Barr Virus-Latent Membrane Protein 1 Enhances Autophagy and Cisplatin Resistance in T-Cell Lymphoma |
| title_sort | activation of mek1 2 nrf 2 signaling pathway by epstein barr virus latent membrane protein 1 enhances autophagy and cisplatin resistance in t cell lymphoma |
| url | http://dx.doi.org/10.1155/2021/6668947 |
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