Nanog, in Cooperation with AP1, Increases the Expression of E6/E7 Oncogenes from HPV Types 16/18

Autor: Patricio Gariglio-Vidal, Marcela Lizano, Helga M. Lopez-Carbajal, Miriam Guido-Jiménez, Yakelin Díaz-Tejeda, Alejandro García-Carrancá, Rocío Méndez-Martínez, Alfredo Amador-Molina
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Homeobox protein NANOG
Gene Expression Regulation
Viral
Transcriptional Activation
Papillomavirus E7 Proteins
HPV16/18
Uterine Cervical Neoplasms
Biology
Microbiology
Nanog
Article
03 medical and health sciences
0302 clinical medicine
Transcription (biology)
Virology
Cell Line
Tumor
Humans
Promoter Regions
Genetic
Transcription factor
AP1
reproductive and urinary physiology
Human papillomavirus 16
Human papillomavirus 18
c-jun
c-Jun
Papillomavirus Infections
Nanog Homeobox Protein
Oncogene Proteins
Viral
QR1-502
female genital diseases and pregnancy complications
DNA-Binding Proteins
Repressor Proteins
Transcription Factor AP-1
AP-1 transcription factor
030104 developmental biology
Infectious Diseases
Regulatory sequence
E6/E7
030220 oncology & carcinogenesis
embryonic structures
LCR
Host-Pathogen Interactions
Cancer research
Female
Stem cell
biological phenomena
cell phenomena
and immunity
Chromatin immunoprecipitation
Zdroj: Viruses
Volume 13
Issue 8
Viruses, Vol 13, Iss 1482, p 1482 (2021)
ISSN: 1999-4915
Popis: Persistent infections with some types of human papillomavirus (HPV) constitute the major etiological factor for cervical cancer development. Nanog, a stem cell transcription factor has been shown to increase during cancer progression. We wanted to determine whether Nanog could modulate transcription of E6 and E7 oncogenes. We used luciferase reporters under the regulation of the long control region (LCR) of HPV types 16 and 18 (HPV16/18) and performed RT-qPCR. We found that Nanog increases activity of both viral regulatory regions and elevates endogenous E6/E7 mRNA levels in cervical cancer-derived cells. We demonstrated by in vitro mutagenesis that changes at Nanog-binding sites found in the HPV18 LCR significantly inhibit transcriptional activation. Chromatin immunoprecipitation (ChIP) assays showed that Nanog binds in vivo to the HPV18 LCR, and its overexpression increases its binding as well as that of c-Jun. Surprisingly, we observed that mutation of AP1-binding sites also affect Nanog’s ability to activate transcription, suggesting cooperation between the two factors. We searched for putative Nanog-binding sites in the LCR of several HPVs and surprisingly found them only in those types associated with cancer development. Our study shows, for the first time, a role for Nanog in the regulation of E6/E7 transcription of HPV16/18.
Databáze: OpenAIRE
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