Human papillomavirus16 E6 but not E7 upregulates GLUT1 expression in lung cancer cells by upregulating thioredoxin expression
Background and objective: E6 and E7 proteins in human papillomavirus (HPV) 16 are major oncogenes in several types of tumors, including lung cancer. Previous studies have demonstrated that both E6 and E7 oncoproteins can upregulate GLUT1 protein and mRNA expression levels in lung cancer cells. Thus,...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721363/ https://www.ncbi.nlm.nih.gov/pubmed/34939468 http://dx.doi.org/10.1177/15330338211067111 |
_version_ | 1784625323912986624 |
---|---|
author | Gao, Zi-Yu Gu, Na-Jin Wu, Ming-Zhe Wang, Shi-Yu Xu, Hong-Tao Li, Qing-Chang Wu, Guang-Ping |
author_facet | Gao, Zi-Yu Gu, Na-Jin Wu, Ming-Zhe Wang, Shi-Yu Xu, Hong-Tao Li, Qing-Chang Wu, Guang-Ping |
author_sort | Gao, Zi-Yu |
collection | PubMed |
description | Background and objective: E6 and E7 proteins in human papillomavirus (HPV) 16 are major oncogenes in several types of tumors, including lung cancer. Previous studies have demonstrated that both E6 and E7 oncoproteins can upregulate GLUT1 protein and mRNA expression levels in lung cancer cells. Thus, the present study aimed to investigate the main differences in the molecular mechanisms of GLUT1 expression regulated by E6 and E7. Methods: The double directional genetic manipulation and immunofluorescence were performed to explore the molecular mechanism of E6 or E7 upregulating the expression of GLUT1 in H1299 and A549 cell lines. Results: The overexpression of E6 in well-established lung cancer cell lines upregulated thioredoxin (Trx) protein expression. Notably, plasmid transfection or small interfering RNA transfection with E7 had no regulatory effect on Trx expression. As an important disulfide reductase of the intracellular antioxidant system, Trx plays important role in maintaining oxidative stress balance and protecting cells from oxidative damage. The overexpression of Trx increased the activation of NF-κB by upregulating p65 expression and promoting p65 nuclear translocation, and further upregulated GLUT1 protein and mRNA expression levels. The results of the present study demonstrated that E6, but not E7, upregulated GLUT1 expression in lung cancer cells by activating NF-κB due to the participation of Trx. Conclusion: These results suggest that Trx plays an important role in the pathogenesis of HPV-associated lung cancer, and propose a novel therapeutic target for HPV-associated lung cancer. |
format | Online Article Text |
id | pubmed-8721363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-87213632022-01-04 Human papillomavirus16 E6 but not E7 upregulates GLUT1 expression in lung cancer cells by upregulating thioredoxin expression Gao, Zi-Yu Gu, Na-Jin Wu, Ming-Zhe Wang, Shi-Yu Xu, Hong-Tao Li, Qing-Chang Wu, Guang-Ping Technol Cancer Res Treat Original Article Background and objective: E6 and E7 proteins in human papillomavirus (HPV) 16 are major oncogenes in several types of tumors, including lung cancer. Previous studies have demonstrated that both E6 and E7 oncoproteins can upregulate GLUT1 protein and mRNA expression levels in lung cancer cells. Thus, the present study aimed to investigate the main differences in the molecular mechanisms of GLUT1 expression regulated by E6 and E7. Methods: The double directional genetic manipulation and immunofluorescence were performed to explore the molecular mechanism of E6 or E7 upregulating the expression of GLUT1 in H1299 and A549 cell lines. Results: The overexpression of E6 in well-established lung cancer cell lines upregulated thioredoxin (Trx) protein expression. Notably, plasmid transfection or small interfering RNA transfection with E7 had no regulatory effect on Trx expression. As an important disulfide reductase of the intracellular antioxidant system, Trx plays important role in maintaining oxidative stress balance and protecting cells from oxidative damage. The overexpression of Trx increased the activation of NF-κB by upregulating p65 expression and promoting p65 nuclear translocation, and further upregulated GLUT1 protein and mRNA expression levels. The results of the present study demonstrated that E6, but not E7, upregulated GLUT1 expression in lung cancer cells by activating NF-κB due to the participation of Trx. Conclusion: These results suggest that Trx plays an important role in the pathogenesis of HPV-associated lung cancer, and propose a novel therapeutic target for HPV-associated lung cancer. SAGE Publications 2021-12-23 /pmc/articles/PMC8721363/ /pubmed/34939468 http://dx.doi.org/10.1177/15330338211067111 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Article Gao, Zi-Yu Gu, Na-Jin Wu, Ming-Zhe Wang, Shi-Yu Xu, Hong-Tao Li, Qing-Chang Wu, Guang-Ping Human papillomavirus16 E6 but not E7 upregulates GLUT1 expression in lung cancer cells by upregulating thioredoxin expression |
title | Human papillomavirus16 E6 but not E7 upregulates GLUT1 expression in lung cancer cells by upregulating thioredoxin expression |
title_full | Human papillomavirus16 E6 but not E7 upregulates GLUT1 expression in lung cancer cells by upregulating thioredoxin expression |
title_fullStr | Human papillomavirus16 E6 but not E7 upregulates GLUT1 expression in lung cancer cells by upregulating thioredoxin expression |
title_full_unstemmed | Human papillomavirus16 E6 but not E7 upregulates GLUT1 expression in lung cancer cells by upregulating thioredoxin expression |
title_short | Human papillomavirus16 E6 but not E7 upregulates GLUT1 expression in lung cancer cells by upregulating thioredoxin expression |
title_sort | human papillomavirus16 e6 but not e7 upregulates glut1 expression in lung cancer cells by upregulating thioredoxin expression |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721363/ https://www.ncbi.nlm.nih.gov/pubmed/34939468 http://dx.doi.org/10.1177/15330338211067111 |
work_keys_str_mv | AT gaoziyu humanpapillomavirus16e6butnote7upregulatesglut1expressioninlungcancercellsbyupregulatingthioredoxinexpression AT gunajin humanpapillomavirus16e6butnote7upregulatesglut1expressioninlungcancercellsbyupregulatingthioredoxinexpression AT wumingzhe humanpapillomavirus16e6butnote7upregulatesglut1expressioninlungcancercellsbyupregulatingthioredoxinexpression AT wangshiyu humanpapillomavirus16e6butnote7upregulatesglut1expressioninlungcancercellsbyupregulatingthioredoxinexpression AT xuhongtao humanpapillomavirus16e6butnote7upregulatesglut1expressioninlungcancercellsbyupregulatingthioredoxinexpression AT liqingchang humanpapillomavirus16e6butnote7upregulatesglut1expressioninlungcancercellsbyupregulatingthioredoxinexpression AT wuguangping humanpapillomavirus16e6butnote7upregulatesglut1expressioninlungcancercellsbyupregulatingthioredoxinexpression |