Digital RNA Sequencing of Human Epidermal Keratinocytes Carrying Human Papillomavirus Type 16 E7

High-risk human papillomavirus (HPV) infections are the predominant cause of cervical cancer and its early gene E7 plays an important role in cellular proliferation and cell-cycle progression. While tremendous progress has been made in exploring the molecular mechanisms in late tumorigenesis, many p...

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Main Authors: Chunting Hua, Jiang Zhu, Boya Zhang, Siyuan Sun, Yinjing Song, Stijn van der Veen, Hao Cheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-08-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fgene.2020.00819/full
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author Chunting Hua
Jiang Zhu
Boya Zhang
Siyuan Sun
Yinjing Song
Stijn van der Veen
Stijn van der Veen
Hao Cheng
author_facet Chunting Hua
Jiang Zhu
Boya Zhang
Siyuan Sun
Yinjing Song
Stijn van der Veen
Stijn van der Veen
Hao Cheng
author_sort Chunting Hua
collection DOAJ
description High-risk human papillomavirus (HPV) infections are the predominant cause of cervical cancer and its early gene E7 plays an important role in cellular proliferation and cell-cycle progression. While tremendous progress has been made in exploring the molecular mechanisms in late tumorigenesis, many pathways showing how HPV deregulates host gene expression in early inapparent infections and early tumorigenesis still remain undefined. Digital RNA sequencing was performed and a total of 195 differentially expressed genes were identified between the HPV16 E7-transfected NHEKs and control cells (p < 0.05, fold-change > 2). GO enrichment showed that HPV16 E7 primarily affected processes involved in anti-viral and immune responses, while KEGG pathway analysis showed enrichment of gene clusters of associated with HPV infection and MAPK signaling. Of the differentially expressed genes, IFI6, SLC39A9 and ZNF185 showed a strong correlation with tumor progression and patient survival in the OncoLnc database while roles for AKAP12 and DUSP5 in carcinogenesis and poor prognosis have previously been established for other cancer types. Our study identified several novel HPV16 E7-regulated candidate genes with putative functions in tumorigenesis, thus providing new insights into HPV persistence in keratinocytes and early onset of tumorigenesis.
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spelling doaj.art-5059396f1060491ca365c7358101fb2c2022-12-21T18:54:16ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-08-011110.3389/fgene.2020.00819557036Digital RNA Sequencing of Human Epidermal Keratinocytes Carrying Human Papillomavirus Type 16 E7Chunting Hua0Jiang Zhu1Boya Zhang2Siyuan Sun3Yinjing Song4Stijn van der Veen5Stijn van der Veen6Hao Cheng7Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Microbiology and Parasitology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaHigh-risk human papillomavirus (HPV) infections are the predominant cause of cervical cancer and its early gene E7 plays an important role in cellular proliferation and cell-cycle progression. While tremendous progress has been made in exploring the molecular mechanisms in late tumorigenesis, many pathways showing how HPV deregulates host gene expression in early inapparent infections and early tumorigenesis still remain undefined. Digital RNA sequencing was performed and a total of 195 differentially expressed genes were identified between the HPV16 E7-transfected NHEKs and control cells (p < 0.05, fold-change > 2). GO enrichment showed that HPV16 E7 primarily affected processes involved in anti-viral and immune responses, while KEGG pathway analysis showed enrichment of gene clusters of associated with HPV infection and MAPK signaling. Of the differentially expressed genes, IFI6, SLC39A9 and ZNF185 showed a strong correlation with tumor progression and patient survival in the OncoLnc database while roles for AKAP12 and DUSP5 in carcinogenesis and poor prognosis have previously been established for other cancer types. Our study identified several novel HPV16 E7-regulated candidate genes with putative functions in tumorigenesis, thus providing new insights into HPV persistence in keratinocytes and early onset of tumorigenesis.https://www.frontiersin.org/article/10.3389/fgene.2020.00819/fullhuman epidermal keratinocyteshuman papillomavirus type 16E7 geneAKAP12DUSP5MAPK signaling pathway
spellingShingle Chunting Hua
Jiang Zhu
Boya Zhang
Siyuan Sun
Yinjing Song
Stijn van der Veen
Stijn van der Veen
Hao Cheng
Digital RNA Sequencing of Human Epidermal Keratinocytes Carrying Human Papillomavirus Type 16 E7
Frontiers in Genetics
human epidermal keratinocytes
human papillomavirus type 16
E7 gene
AKAP12
DUSP5
MAPK signaling pathway
title Digital RNA Sequencing of Human Epidermal Keratinocytes Carrying Human Papillomavirus Type 16 E7
title_full Digital RNA Sequencing of Human Epidermal Keratinocytes Carrying Human Papillomavirus Type 16 E7
title_fullStr Digital RNA Sequencing of Human Epidermal Keratinocytes Carrying Human Papillomavirus Type 16 E7
title_full_unstemmed Digital RNA Sequencing of Human Epidermal Keratinocytes Carrying Human Papillomavirus Type 16 E7
title_short Digital RNA Sequencing of Human Epidermal Keratinocytes Carrying Human Papillomavirus Type 16 E7
title_sort digital rna sequencing of human epidermal keratinocytes carrying human papillomavirus type 16 e7
topic human epidermal keratinocytes
human papillomavirus type 16
E7 gene
AKAP12
DUSP5
MAPK signaling pathway
url https://www.frontiersin.org/article/10.3389/fgene.2020.00819/full
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