HPV16 E6 Promotes the Progression of HPV Infection-Associated Cervical Cancer by Upregulating Glucose-6-Phosphate Dehydrogenase Expression

Cervical cancer, which is significantly associated with high-risk human papillomavirus (HPV) infection, currently ranks the fourth most common cancer among women worldwide. Previous literature reported that the elevated expression of G6PD was significantly correlated with the occurrence and deterior...

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Main Authors: Ye-Fei Chang, Guo-Ji Yan, Guang-Cai Liu, Ying Hong, Hong-Lan Chen, Shui Jiang, Yong Zhong, Yan-Bin Xiyang, Tao Hu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-10-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.718781/full
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author Ye-Fei Chang
Guo-Ji Yan
Guang-Cai Liu
Ying Hong
Hong-Lan Chen
Shui Jiang
Yong Zhong
Yan-Bin Xiyang
Tao Hu
author_facet Ye-Fei Chang
Guo-Ji Yan
Guang-Cai Liu
Ying Hong
Hong-Lan Chen
Shui Jiang
Yong Zhong
Yan-Bin Xiyang
Tao Hu
author_sort Ye-Fei Chang
collection DOAJ
description Cervical cancer, which is significantly associated with high-risk human papillomavirus (HPV) infection, currently ranks the fourth most common cancer among women worldwide. Previous literature reported that the elevated expression of G6PD was significantly correlated with the occurrence and deterioration of human cervical cancer, especially with the cervical cancer with HPV16 and HPV18 infection. In this study, we verified that G6PD expression has a strong positive correlation with HPV16 E6 levels in cervical cancer tissues and cells. In addition, regulating the expression of HPV16 E6 significantly affected the proliferation, apoptosis, migration, and invasion in the cervical cancer HeLa cells, as well as the transcript and protein levels of G6PD. The luciferase reporter assay and ChIP assay proved that HPV16 E6 stimulated the transcription of G6PD mRNA and subsequently enhanced the expression of G6PD through directly binding to the specific sites in the promoter of G6PD. Our findings reveal that HPV16 E6 is a novel regulatory factor of G6PD. Furthermore, by regulating the expression of G6PD, HPV16 E6 might promote the proliferation and migration potential, and inhibit apoptosis of cervical cancer cells, which ultimately contributed to the progression and metastasis of cervical cancer.
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spelling doaj.art-b2155945d77f40739f23749fa7a7d4f92022-12-21T18:37:43ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-10-011110.3389/fonc.2021.718781718781HPV16 E6 Promotes the Progression of HPV Infection-Associated Cervical Cancer by Upregulating Glucose-6-Phosphate Dehydrogenase ExpressionYe-Fei Chang0Guo-Ji Yan1Guang-Cai Liu2Ying Hong3Hong-Lan Chen4Shui Jiang5Yong Zhong6Yan-Bin Xiyang7Tao Hu8Department of Laboratory Medicine, The Third People’s Hospital of Yunnan Province, Kunming, ChinaInstitute of Neuroscience, Basic Medical College, Kunming Medical University, Kunming, ChinaDepartment of Laboratory Medicine, The Third People’s Hospital of Yunnan Province, Kunming, ChinaDepartment of Laboratory Medicine, The Third People’s Hospital of Yunnan Province, Kunming, ChinaDepartment of Laboratory Medicine, The Third People’s Hospital of Yunnan Province, Kunming, ChinaDepartment of Laboratory Medicine, The Third People’s Hospital of Yunnan Province, Kunming, ChinaDepartment of Laboratory Medicine, The Third People’s Hospital of Yunnan Province, Kunming, ChinaInstitute of Neuroscience, Basic Medical College, Kunming Medical University, Kunming, ChinaDepartment of Laboratory Medicine, The Third People’s Hospital of Yunnan Province, Kunming, ChinaCervical cancer, which is significantly associated with high-risk human papillomavirus (HPV) infection, currently ranks the fourth most common cancer among women worldwide. Previous literature reported that the elevated expression of G6PD was significantly correlated with the occurrence and deterioration of human cervical cancer, especially with the cervical cancer with HPV16 and HPV18 infection. In this study, we verified that G6PD expression has a strong positive correlation with HPV16 E6 levels in cervical cancer tissues and cells. In addition, regulating the expression of HPV16 E6 significantly affected the proliferation, apoptosis, migration, and invasion in the cervical cancer HeLa cells, as well as the transcript and protein levels of G6PD. The luciferase reporter assay and ChIP assay proved that HPV16 E6 stimulated the transcription of G6PD mRNA and subsequently enhanced the expression of G6PD through directly binding to the specific sites in the promoter of G6PD. Our findings reveal that HPV16 E6 is a novel regulatory factor of G6PD. Furthermore, by regulating the expression of G6PD, HPV16 E6 might promote the proliferation and migration potential, and inhibit apoptosis of cervical cancer cells, which ultimately contributed to the progression and metastasis of cervical cancer.https://www.frontiersin.org/articles/10.3389/fonc.2021.718781/fullE6 proteinhuman papillomavirusglucose-6-phosphate dehydrogenasecervical cancerHPV16 E6
spellingShingle Ye-Fei Chang
Guo-Ji Yan
Guang-Cai Liu
Ying Hong
Hong-Lan Chen
Shui Jiang
Yong Zhong
Yan-Bin Xiyang
Tao Hu
HPV16 E6 Promotes the Progression of HPV Infection-Associated Cervical Cancer by Upregulating Glucose-6-Phosphate Dehydrogenase Expression
Frontiers in Oncology
E6 protein
human papillomavirus
glucose-6-phosphate dehydrogenase
cervical cancer
HPV16 E6
title HPV16 E6 Promotes the Progression of HPV Infection-Associated Cervical Cancer by Upregulating Glucose-6-Phosphate Dehydrogenase Expression
title_full HPV16 E6 Promotes the Progression of HPV Infection-Associated Cervical Cancer by Upregulating Glucose-6-Phosphate Dehydrogenase Expression
title_fullStr HPV16 E6 Promotes the Progression of HPV Infection-Associated Cervical Cancer by Upregulating Glucose-6-Phosphate Dehydrogenase Expression
title_full_unstemmed HPV16 E6 Promotes the Progression of HPV Infection-Associated Cervical Cancer by Upregulating Glucose-6-Phosphate Dehydrogenase Expression
title_short HPV16 E6 Promotes the Progression of HPV Infection-Associated Cervical Cancer by Upregulating Glucose-6-Phosphate Dehydrogenase Expression
title_sort hpv16 e6 promotes the progression of hpv infection associated cervical cancer by upregulating glucose 6 phosphate dehydrogenase expression
topic E6 protein
human papillomavirus
glucose-6-phosphate dehydrogenase
cervical cancer
HPV16 E6
url https://www.frontiersin.org/articles/10.3389/fonc.2021.718781/full
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