scholarly journals HPV16 E6 Gene Polymorphisms and the Functions of the Mutation Site in Cervical Cancer Among Uygur and Han Women in Xinjiang

2021 ◽  
Author(s):  
Huizhen Xin ◽  
Zhenzhen Pan ◽  
Xiangyi Zhe ◽  
Chunhe Zhang ◽  
Hongtao Li ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cellular Proliferation ◽  
Hpv Infection ◽  
Eukaryotic Expression ◽  
Expression Vectors ◽  
Migration And Invasion ◽  
Genotype Distribution ◽  
Mutation Site ◽  
Hpv16 E6 ◽  
E6 Gene

Abstract Background: To investigate the genotype distribution of human papillomavirus (HPV) in infected Uygur and Han women in Xinjiang; analyze the HPV16 E6 gene polymorphism site and relationship with the development of cervical cancer.Methods: The HPV16 E6 sequence was analyzed using the European standard prototype to perform an evolutionary tree. HPV16 E6-295T/350T, 295G/350G, and 295T/350G GV230 vectors were stably transfected into cervical cancer C33A cells to analyze the cell proliferation, migration and invasion, apoptosis by CCK8 and clonogenic assays, transwell and cell scratch assays, FACS experiments. Results: The total HPV infection rate was 26.390% (760/2879), whereas the Uygur 22.87% (196/857) and the Han was 27.89% (564/2022) (P < 0.05). Among 110 mutations, 65 cases of E6 genes were mutated at nucleotide 350 (T350G) with the leucine changing to valine (L83V). Moreover, there were 7 cases of E6 gene mutated at nucleotide 295 (T295G) with aspartic changing to glutamic (D64E). When E6 vector(s) of mutations sites were transfected into C33A cells, they were found to promote cellular proliferation, migration, invasion, and inhibit apoptosis. The 295T/350G had the strongest effect on C33A cells and 295G/350G was significantly stronger than 295T/350T (P < 0.05).Conclusions: The positive HPV infection rates differed between the Uygur and Han in Xinjiang, and the genotype distribution of infection was different. After transfecting C33A cells with different eukaryotic expression vectors, the 295T/350G mutation site promoted the proliferation，migration, and invasion of C33A cells to a greater extent than 295G/350G; however, 295G/350G had a stronger effect than 295T/350T.

scholarly journals HPV16 E6 gene polymorphisms and the functions of the mutation site in cervical cancer among Uygur and Han women in Xinjiang

2020 ◽  
Author(s):  
Huizhen Xin ◽  
Zhenzhen Pan ◽  
Xiangyi Zhe ◽  
Dongmei Li ◽  
Chunhe Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Infection Rate ◽  
Hpv Infection ◽  
Eukaryotic Expression ◽  
Migration And Invasion ◽  
Genotype Distribution ◽  
Mutation Site ◽  
Hpv16 E6 ◽  
E6 Gene ◽  
C33a Cell

Abstract Objective : This study aimed to: 1) investigate the status and genotype distribution of human papillomavirus (HPV) in infected Uygur and Han women in Xinjiang; 2) elucidate the variation of the HPV16 E6 gene sequence in the cervix of Uygur and Han women in Xinjiang; and 3) analyze the HPV16 E6 gene polymorphism site and relationship with the development of cervical cancer. Methods : A total of 2879 samples of cervical mucus from the exfoliated cells of Uygur and Han women were collected for an epidemiological analysis of HPV. Genomic DNA was extracted from the cervical HPV16-positive tissues of 110 Uygur and Han women, and E6 was amplified by PCR and sequenced. The HPV16 E6 sequence was analyzed using the European standard as the prototype, and an evolutionary tree analysis was performed. HPV16 E6-295T/350T-GV230, HPV16 E6-295G/350G-GV230, and HPV16 E6-295T/350G-GV230 were stably transfected into human cervical cancer C33A cells. HPV16 E6 protein expression was confirmed using a direct immunofluorescence assay. CCK8 and clonogenic assays were used to analyze C33A cell proliferation. Both a transwell and cell scratch assay were used to study C33A cell migration and invasion. C33A cell apoptosis was analyzed using FACS experiments. SPSS17.0 statistical software was used for statistical data processing. P < 0.05 was considered statistically significant. Results : The total HPV infection rate was 26.390% (760/2879), whereas the Uygur infection rate was 22.87% (196/857) and the Han infection rate was 27.89% (564/2022) (P < 0.05). HPV16, HPV 52, and HPV 53 were associated with higher detection rates in Uygur, whereas HPV16, HPV52, and HPV58 exhibited a higher detection rate in Han. HPV-infected women from Uygur and Han commonly exhibited a single infection. A total of 14 mutation sites were identified in the HPV16 E6 gene by sequencing 110 HPV16-positive samples, including eight missense and six synonymous mutations. Among these, 65 cases of E6 genes were mutated at nucleotide 350 (T350G) with the corresponding amino acids changing from leucine to valine (L83V) and a mutation rate of 59.09%. Moreover, there were seven cases of an E6 gene mutation at nucleotide 295 (T295G) with corresponding amino acid changes from aspartic to glutamic (D64E) and a mutation rate of 6.36%. It is important to note that these seven cases of HPV16 E6 T295G mutations were accompanied by the E6 T350G mutation. Phylogenetic analysis showed that there were HPV16 European (Ep), European variant (E), and three Asian (As) types in Uygur and Han women. No African (Af) and Asian American (AA) types were observed. When HPV16 E6 295T/350T, 295G/350G, and 295T/350G GV230 eukaryotic expression vector(s) were stably transfected into cervical cancer C33A cells, they were found to promote cellular proliferation, migration, invasion, and inhibit apoptosis. The 295T/350G-GV230 had the strongest effect on C33A cells and 295G/350G-GV230 was significantly stronger than 295T/350T-GV230 (P < 0.05). Conclusions : The positive HPV infection rates differed between the Uygur and Han groups in Xinjiang, and the genotype distribution of HPV infection was different. Between the Uygur and Han women in Xinjiang, the main types of HPV16 infection were European (E) and Asian (As). After stably transfecting C33A cells with a eukaryotic expression vector for different polymorphism sites (295T/350T, 295G/350G, and 295T/350G), the 295T/350G mutation site promoted the proliferation，migration, and invasion of C33A cells to a greater extent than 295G/350G; however, 295G/350G had a stronger effect than 295T/350T.

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

2021 ◽  
Vol 11 ◽  
Author(s):  
Ye-Fei Chang ◽  
Guo-Ji Yan ◽  
Guang-Cai Liu ◽  
Ying Hong ◽  
Hong-Lan Chen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Hpv Infection ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Strong Positive Correlation ◽  
Hpv16 E6 ◽  
Protein Levels ◽  
Cervical Cancer Cells ◽  
Elevated Expression ◽  
And Migration

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.

scholarly journals miR-4454 up-regulated by HPV16 E6/E7 promotes invasion and migration by targeting ABHD2/NUDT21 in cervical cancer

2019 ◽  
Author(s):  
Hui Wang ◽  
Hui Hu ◽  
Zhenzhao Luo ◽  
Shuiyi Liu ◽  
Wangze Wu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Invasion ◽  
Tumor Suppressor Genes ◽  
Target Gene ◽  
Migration And Invasion ◽  
Caski Cell ◽  
Hpv16 E6 ◽  
Invasion And Migration ◽  
C33a Cell ◽  
And Migration

Abstract The abnormal expression of HPV16 E6/E7 activates oncogenes and/or inactivates tumor suppressor genes, resulting in the selective growth and malignant transformation of cancer cells. miR-4454 was selected by sequencing due to its abnormal high expression in HPV16 E6/E7 positive CaSki cell compared with HPV16 E6/E7 negative C33A cell. Overexpression of miR-4454 enhances cervical cancer cell invasion and migration. ABHD2 and NUDT21 is identified as a target gene of miR-4454.The effects of ABHD2 and NUDT21 on migration and invasion of CaSki and C33A cells were determined. The dual luciferase and RT-qPCR assays confirmed that miR-4454 might regulate its targets ABHD2 and NUDT21 to promote the proliferation, invasion and migration, whereas, inhibit the apoptosis in CaSki and C33A cells.

scholarly journals Distribution and Prevalence of High-Risk Human Papillomavirus Genotypes in Cervical Specimens

2020 ◽  
Vol 25 (3) ◽  
pp. 325-331
Author(s):  
Erkan Özmen ◽  
Ülkü Altoparlak ◽  
Muhammet Hamidullah Uyanık ◽  
Abdulkadir Gülen
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Age Groups ◽  
Hpv Infection ◽  
High Rate ◽  
Genotype Distribution ◽  
Hpv Dna ◽  
Hpv Test ◽  
Significant Difference ◽  
Hpv Types

Introduction: Human papillomavirus (HPV) is frequently a sexually transmitted virus and can cause cervical cancer in women. Cervical cancer is the second most common type of cancer among the developing countries. In this study, cervical HPV DNA positivity and genotype distributions were investigated in female patients living in our region and the results were compared with different studies. Materials and Methods: Between 1 July, 2017 and 1 March, 2019, 433 cervical swabs were sent to Ataturk University, Medical Faculty Hospital, Medical Microbiology Laboratory due to suspicion of HPV. Swab samples were evaluated for HPV virus using molecular (Polymerase Chain Reaction-PCR) methods. For this purpose, Xpert HPV Test (Cepheid, Inc, Sunnyvale, CA) was used to identify HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 t in a single sample. Results: Mean age of the patients ranged from 20 to 69 years, with a mean of 39.8 years (± 10.0). Positivity was detected in 62 of the 433 patients. Mean age of the positive patients was 40.2 years (± 11.3). When the positive patients were examined in terms of HPV types, the presence of HPV 16 was observed with a rate of 25.6%, while the HPV 18/45 types were found to be 9.0% in total. When patients were evaluated according to age groups, HPV DNA positivity was highest in the 25-34 age group with 38.7%. In our statistical study, there was no significant difference in HPV DNA positivity rate between the ages of 35 and under 35 years. Conclusion: This study demonstrates the prevalence and viral genotype distribution of HPV infection in women in Erzurum region. HPV type 16 is seen with a high rate in our region.

TP53 Codon 72 Polymorphism does not Affect Risk of Cervical Cancer in Patients from the Gambia

2003 ◽  
Vol 18 (4) ◽  
pp. 280-283 ◽  
Author(s):  
G. Tanara ◽  
C. Falugi ◽  
A. Cesario ◽  
S. Margaritora ◽  
P. Russo ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Geographical Area ◽  
Population Sample ◽  
Hpv Infection ◽  
The Gambia ◽  
Control Group ◽  
Genotype Distribution ◽  
Hpv 16 ◽  
Codon 72 ◽  
Tp53 Polymorphism

Aims A case-control study was performed to investigate the relationship between cervical cancer and TP53 polymorphism at codon 72 in young black African women from The Gambia. Materials and Methods The TP53 polymorphism at codon 72 was examined by PCR amplification and SSCP analysis in 40 patients with primary cervical cancer and in 20 healthy women of the same age and from the same geographical area. The occurrence of TP53 polymorphism in combination with the HPV-16 E6 genotype (assayed by PCR) was evaluated. Results The distribution of TP53 genotypes in cervical cancer patients and in the control group was not statistically different (p=0.45) and homozygosity for argine at residue 72 was not associated with cervical cancer (odds ratio: 1.24; 95% confidence interval 0.21-9.16). Similarly, a different genotype distribution, cervical cancer and presence of HPV-16 E6 were not observed. Conclusions These results cannot rule out an association between TP53 polymorphism at codon 72, HPV infection and the etiology of cervical cancer in this population sample.

scholarly journals Analysis of mutations in the E6/E7 oncogenes and L1 gene of human papillomavirus 16 cervical cancer isolates from China

2006 ◽  
Vol 87 (5) ◽  
pp. 1181-1188 ◽  
Author(s):  
Yuping Wu ◽  
Yulong Chen ◽  
Longyu Li ◽  
Guifang Yu ◽  
Ying He ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Patients ◽  
Hpv Infection ◽  
Typing Method ◽  
Hpv16 E6 ◽  
Human Papillomavirus 16 ◽  
Human Papillomavirus Type 16 ◽  
New Variant

Human papillomavirus type 16 (HPV16) has a number of intratypic variants; each has a different geographical distribution and some are associated with enhanced oncogenic potential. Cervical samples were collected from 223 cervical cancer patients and from 196 age-matched control subjects in China. DNA samples were amplified by using primers specific for the E6, E7 and partial L1 regions. Products were sequenced and analysed. It was found by using a PCR–sequence-based typing method that HPV infection rates in China were 92·8 % in cervical cancer patients and 15·8 % in healthy controls. HPV16 was detected in 70·4 % of cervical cancer patients and in 6·1 % of controls. In HPV16-positive cervical cancers, 23·6 % belonged to the prototype, 65·5 % were of the Asian variant, 5·5 % were of African type 1 and 3·6 % were European variants, whilst only one was a new variant that differed from any variant published so far. Prevalences of HPV16 E6 D25E and E113D variants were 67·3 and 9 %, respectively. In addition to D25E and E113D, the following E6 variations were found in this study: R129K, E89Q, S138C, H78Y, L83V and F69L. The results also showed that the prevalences of three hot spots of E7 nucleotide variation, N29S, S63F and a silent variation, nt T846C, were 70·2 % (33/47), 51·1 % (24/47) and 61·7 % (29/47), respectively. The following L1 variations were found in this study: S377A, K387E, E378D, K382E and T379P. It was also found that the average age of Asian variant-positive cervical cancer patients (42·98±10·43 years) was 7·56 years lower than that of prototype-positive patients (50·54±10·91). It is suggested that the high frequency of HPV16 Asian variants might contribute to the high incidence of cervical cancer in China.

scholarly journals Human papillomavirus genotype distribution in cervical intraepithelial neoplasia 2/3 and invasive cervical cancer among Hakka women in southern China

2019 ◽  
Author(s):  
Xiaodong Gu ◽  
Ruiqiang Weng ◽  
Jing Liu ◽  
Sudong Liu
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Southern China ◽  
Invasive Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Histological Diagnosis ◽  
Infection Prevalence ◽  
Genotype Distribution ◽  
Hpv Genotypes

Abstract Background: To investigate HPV genotype distribution in cervical intraepithelial neoplasia 2/3 (CIN2/3) and invasive cervical cancer (ICC) among Hakka women in southern China. Methods: Results of HPV genotypes from women with histological diagnosis of CIN2/3 and ICC were collected from January, 2017 to December, 2018. HPV genotypes were analyzed by flow cytometry method. Association of HPV infection and lesions severity was estimated using prevalence ratio (PR). Results: Overall, 1,408 Hakka women with histological diagnosis of CIN2/3 and ICC were enrolled in this study. HPV infection prevalence was 92.92% in CIN2, 95.77% in CIN3 and 95.88% in ICC. Most frequent genotypes for CIN2 were HPV52 (31.42%), HPV16 (22.12%) and HPV58 (22.12%); for CIN3 were HPV16 (41.90%), HPV52 (20.77%) and HPV58 (18.31%); and for ICC were HPV16 (49.67%), HPV18 (11.25%) and HPV52 (9.80%). PR of HPV16 and HPV33 were significantly higher in CIN3 compared with CIN2 (PR = 2.372, 95%CI = 1.598-3.524; PR = 2.577, 95%CI = 1.250-5.310; respectively). HPV16 and HPV18 prevalence were significantly increasing in SCC compared with CIN3 (PR = 2.517, 95%CI = 1.095-5.786; PR = 2.473, 95%CI = 1.840-3.324; respectively). Most HPV infections were found in women aged 40 – 49 years in CIN2/3 and women aged 50 - 59 years in ICC. Conclusions: This is the first study of genotypes and age specific distribution of HPV infection among Hakka women with CIN2/3 and ICC in southern China. Our results provide available information for HPV vaccine development in China.

scholarly journals ICAT Promotes Cervical Cancer Cell Proliferation, Invasion, Migration and Epithelial‑to‑mesenchymal Transition Through HPV16 E6, E7/ miR-23b-3p/ ICAT Axis

2021 ◽  
Author(s):  
Jing Hu ◽  
Zijiu Sun ◽  
Hui Wang ◽  
Wei Ren ◽  
Yuting Fang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Recombinant Adenovirus ◽  
Cervical Cancer Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Hpv 16 ◽  
Hpv16 E6 ◽  
Mesenchymal Transition

Abstract Background: Human papillomavirus (HPV) 16 plays a crucial role in cervical cancer (CC) development. Previous study reported that inhibitor of β-catenin and TCF (ICAT) is upregulated in CC and promotes cervical tumor progression. Herein, we aimed to investigate the underlying molecular mechanism that HPV16 regulates the expression of ICAT and promotes the CC development. Methods: The expressions of HPV 16 E6, E7 and ICAT were modulated by small interfering RNA and recombinant adenovirus, respectively. qRT-PCR was conducted to detect the mRNA expression of HPV 16 E6, E7, ICAT and miR-23b-3p in SiHa and CasKi cells. Bioinformatics analysis was utilized to predict the potential miRNAs that could bind to the ICAT 3′ untranslated region. Then, the dual luciferase reporter assay was used to confirm that. Cell proliferation ability was detected by CCK-8 assay. Wound healing and Transwell assays were used to observe migration and invasion abilities. Protein expressions were measured with western blot. Results: Results revealed that after knocking down of HPV16 E6, E7, the expression of ICAT decreased, but the expression of miR-23b-3p increased. Besides, miR-23b-3p negatively modulated ICAT expression in HPV16 positive CC cells. Dual luciferase assays confirmed that ICAT was a target gene of miR-23b-3p. Functional experiments showed that the overexpression of miR-23b-3p suppressed malignant behaviors of SiHa and CasKi cells, such as migration, invasion and EMT. Importantly, the overexpression of ICAT counteracted the suppressive effect of miR-23b-3p on HPV16 positive cervical cancer cell. Furthermore, after the knockdown of HPV16 E6 and E7, the inhibition of miR-23b-3p could increase the ICAT expression and rescue the siRNA HPV16 E6, E7-mediated suppressive impact on the aggressiveness of SiHa and CasKi cells.Conclusions: Our study demonstrates that HPV 16 E6, E7/miR-23b-3p/ ICAT axis plays an important role in HPV16 positive CC pathogenesis, which may serve as a promising therapy target for HPV 16-associated cervical cancer.

scholarly journals IRF-1 Inhibits Angiogenic Activity of HPV16 E6 Oncoprotein in Cervical Cancer

2020 ◽  
Vol 21 (20) ◽  
pp. 7622
Author(s):  
Seung Bae Rho ◽  
Seung-Hoon Lee ◽  
Hyun-Jung Byun ◽  
Boh-Ram Kim ◽  
Chang Hoon Lee
Keyword(s):  
Cervical Cancer ◽  
Cell Growth ◽  
Cancer Progression ◽  
Cellular Proliferation ◽  
Endothelial Cell Migration ◽  
Dependent Manner ◽  
P53 Expression ◽  
Angiogenic Activity ◽  
Hpv16 E6 ◽  
E6 Oncoprotein

HPV16 E6 oncoprotein is a member of the human papillomavirus (HPV) family that contributes to enhanced cellular proliferation and risk of cervical cancer progression via viral infection. In this study, interferon regulatory factor-1 (IRF-1) regulates cell growth inhibition and transcription factors in immune response, and acts as an HPV16 E6-binding cellular molecule. Over-expression of HPV16 E6 elevated cell growth by attenuating IRF-1-induced apoptosis and repressing p21 and p53 expression, but activating cyclin D1 and nuclear factor kappa B (NF-κB) expression. The promoter activities of p21 and p53 were suppressed, whereas NF-κB activities were increased by HPV16 E6. Additionally, the cell viability of HPV16 E6 was diminished by IRF-1 in a dose-dependent manner. We found that HPV16 E6 activated vascular endothelial growth factor (VEGF)-induced endothelial cell migration and proliferation as well as phosphorylation of VEGFR-2 via direct interaction in vitro. HPV16 E6 exhibited potent pro-angiogenic activity and clearly enhanced the levels of hypoxia-inducible factor-1α (HIF-1α). By contrast, the loss of function of HPV16 E6 by siRNA-mediated knockdown inhibited the cellular events. These data provide direct evidence that HPV16 E6 facilitates tumour growth and angiogenesis. HPV16 E6 also activates the PI3K/mTOR signalling cascades, and IRF-1 suppresses HPV16 E6-induced tumourigenesis and angiogenesis. Collectively, these findings suggest a biological mechanism underlying the HPV16 E6-related activity in cervical tumourigenesis.

scholarly journals TNFα–308G/A Polymorphism as a Risk Factor for HPV Associated Cervical Cancer in Indian Population

2007 ◽  
Vol 29 (3) ◽  
pp. 249-256
Author(s):  
Indu Kohaar ◽  
Nisha Thakur ◽  
Sudha Salhan ◽  
Swaraj Batra ◽  
Veena Singh ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Direct Sequencing ◽  
Hpv Infection ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Promoter Polymorphisms ◽  
Hpv 16 ◽  
Indian Women ◽  
Control Subjects ◽  
Increased Risk

Background: Investigation of the potential association of single nucleotide polymorphisms (SNPs) at –308 G/A and –238 G/A of Tumor necrosis factor α (TNFα) with susceptibility to HPV-16 associated cervical cancer in Indian women. Methods: The study included 165 histologically confirmed cases with 45 precancer and 120 cancer patients and an equal number (165) of healthy controls with normal cervical cytology. PCR-RFLP was employed to analyze TNFα promoter polymorphisms, which were confirmed by direct sequencing. Both patients and controls were screened for Human Papillomavirus (HPV) infection. Results: The frequency of –308 A allele in TNFα was significantly higher in cases compared with control subjects (21% in cases vs. 9% in controls; p < 0.01), with an odds ratio of 2.7 (95% CI = 1.41–5.15). Also, women carrying A allele for this locus presented 3 times increased susceptibility to HPV 16 infection as evident from carrier genotype distribution between HPV positive cases and control subjects (24% in HPV positive cases vs. 9% in controls; p < 0.01; OR = 3.1; 95% CI = 1.60–6.03). No such association was found for TNFα–238 (G/A) polymorphism with the risk of development of cervical cancer. Conclusion: It suggests that SNP at –308 (G/A) of TNFα promoter may represent an increased risk for HPV infection and development of cervical cancer in Indian women.

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