scholarly journals The Human Papillomavirus (HPV) E6 Oncoprotein Regulates CD40 Expression via the AT-Hook Transcription Factor AKNA

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 521 ◽  
Author(s):  
Joaquin Manzo-Merino ◽  
Alfredo Lagunas-Martínez ◽  
Carla Contreras-Ochoa ◽  
Marcela Lizano ◽  
Leonardo Castro-Muñoz ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Immune Surveillance ◽  
Dependent Manner ◽  
Hpv E6 ◽  
E6 Oncoprotein ◽  
Inflammatory State ◽  
Cervical Cancer Development ◽  
Carcinogenic Process

Persistent infection with high-risk Human Papillomavirus (HR-HPV) is the main requisite for cervical cancer development. Normally, HPV is limited to the site of infection and regulates a plethora of cellular elements to avoid the immune surveillance by inducing an anti-inflammatory state, allowing the progress through the viral cycle and the carcinogenic process. Recent findings suggest that the AT-hook transcriptional factor AKNA could play a role in the development of cervical cancer. AKNA is strongly related to the expression of co-stimulatory molecules such CD40/CD40L to achieve an anti-tumoral immune response. To date, there is no evidence demonstrating the effect of the HPV E6 oncoprotein on the AT-hook factor AKNA. In this work, minimal expression of AKNA in cervical carcinoma compared to normal tissue was found. We show the ability of E6 from high-risk HPVs 16 and 18 to interact with and down-regulate AKNA as well as its co-stimulatory molecule CD40 in a proteasome dependent manner. We also found that p53 interacts with AKNA and promotes AKNA expression. Our results indicate that the de-regulation of CD40 and AKNA is induced by the HPV E6 oncoprotein, and this event involves the action of p53 suggesting that the axis E6/p53A/AKNA might play an important role in the de-regulation of the immune system during the carcinogenic process induced by HR-HPV.

scholarly journals High-Risk Human Papillomavirus E6 Oncoproteins Interact with 14-3-3ζ in a PDZ Binding Motif-Dependent Manner

2012 ◽  
Vol 87 (3) ◽  
pp. 1586-1595 ◽  
Author(s):  
Siaw Shi Boon ◽  
Lawrence Banks
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Pdz Domain ◽  
Binding Motif ◽  
Dependent Manner ◽  
Hpv E6 ◽  
Hpv Types ◽  
High Risk Hpv ◽  
Hpv 18

ABSTRACTCervical cancer develops through the combined activities of the human papillomavirus (HPV) E6 and E7 oncoproteins. A defining characteristic of E6 oncoproteins derived from cancer-causing HPV types is the presence of a PDZ binding motif (PBM) at the extreme carboxy terminus of the protein which is absent from E6 proteins derived from the so-called low-risk HPV types. Within this PBM is also a protein kinase A (PKA) phospho-acceptor site, which is thought to negatively regulate the association of E6 with its PDZ domain-containing substrates. We can now show that phosphorylation of E6 by PKA and/or AKT confers the ability to interact with 14-3-3ζ. The interaction is direct and specific for the high-risk HPV E6 oncoproteins, although there are significant differences in the efficiencies with which HPV-16, HPV-18, and HPV-31 E6 oncoproteins can associate with 14-3-3ζ; this correlates directly with their respective susceptibilities to phosphorylation by PKA and/or AKT. We demonstrate here that the interaction between E6 and 14-3-3ζ also requires integrity of the E6 PBM, and downregulation of 14-3-3ζ results in a marked reduction in the levels of HPV-18 E6 expression in HeLa cells. Using phospho-specific anti-E6 antibodies, we also demonstrate significant levels of E6 phosphorylationin vivo. These studies redefine the potential relevance of the E6 PBM in the development of cervical cancer, suggesting that interaction with 14-3-3ζ, as well as the more well-established interactions with PDZ domain-containing substrates, is likely to be responsible for the biological activities attributed to this region of the high-risk HPV E6 oncoproteins.

scholarly journals Human Papillomavirus 16 Oncoproteins Downregulate the Expression of miR-148a-3p, miR-190a-5p, and miR-199b-5p in Cervical Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mi-Soon Han ◽  
Jae Myun Lee ◽  
Soo-Nyung Kim ◽  
Jae-Hoon Kim ◽  
Hyon-Suk Kim
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Expression Profiles ◽  
Normal Group ◽  
Cancer Development ◽  
Hybridization Method ◽  
Cancer Group ◽  
Cervical Cancer Development ◽  
High Risk Hpv

Almost all cervical cancers are associated with human papillomavirus (HPV); however, the majority of women infected with this virus do not develop cervical cancer. Therefore, new markers are needed for reliable screening of cervical cancer, especially in relation to HPV infection. We aimed to identify potential microRNAs that may serve as diagnostic markers for cervical cancer development in high-risk HPV-positive patients. We evaluated the microRNA expression profiles in 12 cervical tissues using the hybridization method and verified them by quantitative polymerase chain reaction (qPCR). Finally, we evaluated the effects of HPV16 oncoproteins on the expression of selected microRNAs using cervical cancer cells (CaSki and SiHa) and RNA interference. With the hybridization method, eight microRNAs (miR-9-5p, miR-136-5p, miR-148a-3p, miR-190a-5p, miR-199b-5p, miR-382-5p, miR-597-5p, and miR-655-3p) were found to be expressed differently in the HPV16-positive cervical cancer group and HPV16-positive normal group (fold change ≥ 2). The results of qPCR showed that miR-148a-3p, miR-190a-5p, miR-199b-5p, and miR-655-3p levels significantly decreased in the cancer group compared with the normal group. Upon silencing of HPV16 E5 and E6/E7, miR-148a-3p levels increased in both cell lines. Silencing of E6/E7 in SiHa cells led to the increase in miR-199b-5p and miR-190a-5p levels. Three HPV16 oncoproteins (E5, E6, and E7) downregulate miR-148a-3p, while E6/E7 inhibit miR-199b-5p and miR-190a-5p expression in cervical carcinoma. The three microRNAs, miR-148a-3p, miR-199b-5p, and miR-190a-5p, may be novel diagnostic biomarkers for cervical cancer development in high-risk HPV-positive patients.

scholarly journals Role of Cdk1 in the p53-Independent Abrogation of the Postmitotic Checkpoint by Human Papillomavirus E6

2014 ◽  
Vol 89 (5) ◽  
pp. 2553-2562 ◽  
Author(s):  
Weifang Zhang ◽  
Yingwang Liu ◽  
Ning Zhao ◽  
Hanxiang Chen ◽  
Lijun Qiao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Drug Targets ◽  
Cell Cycle Checkpoints ◽  
Wild Type ◽  
Hpv E6 ◽  
E6 Oncoprotein ◽  
Shed Light

ABSTRACTSpecific types of human papillomavirus (HPV) are strongly associated with the development of cervical carcinoma. The HPV E6 oncoprotein from HPV degrades p53 and abrogates cell cycle checkpoints. Nonetheless, functional p53 has been observed in cervical cancer. We have previously identified a p53-independent function of E6 in attenuating the postmitotic G1-like checkpoint that can lead to polyploidy, an early event during cervical carcinogenesis that predisposes cells to aneuploidy. How E6 promotes cell cycle progression in the presence of p53 and its target, p21, remains a mystery. In this study, we examined the expression of cell cycle-related genes in cells expressing wild-type E6 and the mutant that is defective in p53 degradation but competent in abrogating the postmitotic checkpoint. Our results demonstrated an increase in the steady-state levels of G1- and G2-related cyclins/Cdks in E6-expressing keratinocytes. Interestingly, only Cdk1 remained active in E6 mutant-expressing cells while bypassing the postmitotic checkpoint. Furthermore, the downregulation of Cdk1 impaired the ability of both wild-type and mutant E6 to induce polyploidy. Our study thus demonstrated an important role for Cdk1, which binds p21 with lower affinity than Cdk2, in abrogating the postmitotic checkpoint in E6-expressing cells. We further show that E2F1 is important for E6 to upregulate Cdk1. Moreover, reduced nuclear p21 localization was observed in the E6 mutant-expressing cells. These findings shed light on the mechanisms by which HPV induces genomic instability and hold promise for the identification of drug targets.IMPORTANCEHPV infection is strongly associated with the development of cervical carcinoma. HPV encodes an E6 oncoprotein that degrades the tumor suppressor p53 and abrogates cell cycle checkpoints. Nonetheless, functional p53 has been observed in cervical cancer. We have recently demonstrated a p53-independent abrogation of the postmitotic checkpoint by HPV E6 that induces polyploidy. However, the mechanism is not known. In this study, we provide evidence that Cdk1 plays an important role in this process. Previously, Cdk2 was thought to be essential for the G1/S transition, while Cdk1 only compensated its function in the absence of Cdk2. Our studies have demonstrated a novel role of Cdk1 at the postmitotic G1-like checkpoint in the presence of Cdk2. These findings shed light on the mechanisms by which HPV induces genomic instability and hold promise for the identification of drug targets.

scholarly journals Prevalence and Genotyping of Human Papillomavirus (HPV) in Female with High-Risk Behaviour in Dhaka, Bangladesh

1970 ◽  
Vol 25 (1) ◽  
pp. 65-68 ◽  
Author(s):  
Tahmina Sultana ◽  
Mohsina Huq ◽  
Anadil Alam ◽  
Dipak Kumar Mitra ◽  
Donald James Gomes
Keyword(s):  
Cervical Cancer ◽  
Polymerase Chain Reaction ◽  
Human Papillomavirus ◽  
High Risk ◽  
General Population ◽  
Sex Workers ◽  
Chain Reaction ◽  
Hpv Types ◽  
Polymerase Chain ◽  
High Risk Hpv

In developing countries, cervical cancer is the most common cause of cancer related to mortality in women. But the epidemiology of human papillomavirus (HPV) in different areas of Bangladesh is largely unknown both in risk groups and in the general population. The objective of the present study was to determine the risk factors associated with having HPV and the prevalence of high-risk HPV types among women with highrisk behaviour and to assess its potential impact on preventive strategies as the sex workers are at increased risk for sexually transmitted infections (STI), HPV and hence cervical cancer. Cervical swab from 293 sex workers in Dhaka City between August and September 2003 and between February 2005 and May 2006 were screened for HPV DNA using an HPV short fragment (E6) polymerase chain reaction (PCR) based assay. HPV positive samples were genotyped with nested multiplex polymerase chain reaction (NMPCR) for the highrisk types. The overall HPV prevalence in sex workers was 75.8%, whereas for the high risk type it was 49.8%. Prevalence of single genotype and multiple types of HPV was 33.1 and 16.7% respectively. The most prevalent high-risk HPV types, in order of prevalence rate, were HPV16, HPV18, HPV58, HPV45, HPV31 and HPV33. Both HPV 16 and HPV 18 were present in 21% of the cases. Targeting HPV 16 and 18 with prophylactic vaccines could possibly have an important impact on the incidence of invasive cervical carcinoma in this group of women. Primary prevention and cervical cancer screening programmes should be optimized more and run yearly among the general population. It is proposed to screen sex workers when they enter prostitution regardless of their age. Keywords: Human papillomavirus (HPV); High-risk HPV types; Cervical cancer; Sex workersDOI: http://dx.doi.org/10.3329/bjm.v25i1.4861 Bangladesh J Microbiol, Volume 25, Number 1, June 2008, pp 65-68

scholarly journals Human papillomavirus detection in cervical scrapes from women attended in the Family Health Program

2014 ◽  
Vol 22 (1) ◽  
pp. 100-107 ◽  
Author(s):  
Everton Faccini Augusto ◽  
Larissa Silva dos Santos ◽  
Ledy do Horto dos Santos Oliveira
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Health Program ◽  
Vaccine Coverage ◽  
Family Health ◽  
Polymorphism Analysis ◽  
Genotype Distribution ◽  
Cross Sectional Survey ◽  
Family Health Program

OBJECTIVES: to survey the prevalence of human papillomavirus, associated risk factors and genotype distribution in women who were referred to cervical cancer screening when attended in a Family Health Program. METHOD: we conducted a cross-sectional survey, investigating 351 women. Polymerase chain reaction for DNA amplification and restriction fragment length polymorphism analysis were used to detect and typify the papillomavirus. RESULTS: virus infection was detected in 8.8% of the samples. Among the 21 different genotypes identified in this study, 14 were high risk for cervical cancer, and the type 16 was the most prevalent type. The infection was associated with women who had non-stable sexual partners. Low risk types were associated with younger women, while the high risk group was linked to altered cytology. CONCLUSION: in this sample attended a Family Health Program, we found a low rate of papillomavirus infection. Virus frequency was associated to sexual behavior. However, the broad range of genotypes detected deserves attention regarding the vaccine coverage, which includes only HPV prevalent types.

scholarly journals Acceptability and feasibility of human papillomavirus vaccination for adolescents in school environments in Libreville

2020 ◽  
Vol 9 (9) ◽  
pp. 3541
Author(s):  
Nathalie L. Ambounda ◽  
Sylvain H. Woromogo ◽  
Olive M. Kenmogne ◽  
Felicite E. Yagata Moussa ◽  
Vicky N. Simo Tekem ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Precancerous Lesions ◽  
Hpv Vaccination ◽  
Immunization Coverage ◽  
Human Papillomaviruses ◽  
Professional Status ◽  
Human Papillomavirus Vaccination ◽  
Cross Sectional

Background: High-risk oncogenic human papillomaviruses (HPV) are the cause of sexually transmitted viral infection. Its persistence is a risk factor for precancerous lesions of the cervix, which will constitute the base of cervical cancer. In the world, the prevalence of high-risk oncogenic HPV is 66.7%, which is higher among women starting their sexual activity.Methods: An analytical cross-sectional study was conducted in high schools in Gabon regarding parents. The variables selected were the socio-cultural and demographic characteristics of the parents, their knowledge of human papillomavirus vaccination and their acceptability of HPV vaccination and finally the feasibility of HPV vaccination. The statistical test used was Pearson's Chi-square, and a difference was considered significant for p<0.05.Results: The majority of parents, 89%, were informed of the existence of cervical cancer. However, 73.4% of them were unaware of the existence of vaccination against cervical cancer. Only 2.4% of parents had vaccinated their daughters against cervical cancer at the time of the study. These parents only 53.4% expressed an interest in vaccinating their daughters in 53.4% of cases. The ability to vaccinate children is associated with the socio-professional status of parents (p˂0.000).Conclusions: The majority of parents approved school-based vaccination against human papillomavirus infections despite its reported cost and lack of information. The integration of anti-HPV vaccination into the expanded programme on immunization in Gabon will improve immunization coverage.

scholarly journals High-risk human papillomavirus in the oral cavity of women with cervical cancer, and their children

2010 ◽  
Vol 7 (1) ◽  
Author(s):  
Rajan Saini ◽  
Tan P Khim ◽  
Sarah A Rahman ◽  
Mazian Ismail ◽  
Thean H Tang
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Oral Cavity
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