Cargando…
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...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235988/ https://www.ncbi.nlm.nih.gov/pubmed/34239803 http://dx.doi.org/10.1155/2021/6668947 |
_version_ | 1783714445322616832 |
---|---|
author | Jia, Xintao He, Qiuyu Zeng, Mei Chen, Yuhua Liu, Yan |
author_facet | Jia, Xintao He, Qiuyu Zeng, Mei Chen, Yuhua Liu, Yan |
author_sort | Jia, Xintao |
collection | PubMed |
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 | Online Article Text |
id | pubmed-8235988 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-82359882021-07-07 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 Jia, Xintao He, Qiuyu Zeng, Mei Chen, Yuhua Liu, Yan Anal Cell Pathol (Amst) Research Article 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. Hindawi 2021-06-18 /pmc/articles/PMC8235988/ /pubmed/34239803 http://dx.doi.org/10.1155/2021/6668947 Text en Copyright © 2021 Xintao Jia et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Jia, Xintao He, Qiuyu Zeng, Mei Chen, Yuhua Liu, Yan 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 | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235988/ https://www.ncbi.nlm.nih.gov/pubmed/34239803 http://dx.doi.org/10.1155/2021/6668947 |
work_keys_str_mv | AT jiaxintao activationofmek12nrf2signalingpathwaybyepsteinbarrviruslatentmembraneprotein1enhancesautophagyandcisplatinresistanceintcelllymphoma AT heqiuyu activationofmek12nrf2signalingpathwaybyepsteinbarrviruslatentmembraneprotein1enhancesautophagyandcisplatinresistanceintcelllymphoma AT zengmei activationofmek12nrf2signalingpathwaybyepsteinbarrviruslatentmembraneprotein1enhancesautophagyandcisplatinresistanceintcelllymphoma AT chenyuhua activationofmek12nrf2signalingpathwaybyepsteinbarrviruslatentmembraneprotein1enhancesautophagyandcisplatinresistanceintcelllymphoma AT liuyan activationofmek12nrf2signalingpathwaybyepsteinbarrviruslatentmembraneprotein1enhancesautophagyandcisplatinresistanceintcelllymphoma |