scholarly journals The Progress of Methylation Regulation in Gene Expression of Cervical Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chunyang Feng ◽  
Junxue Dong ◽  
Weiqin Chang ◽  
Manhua Cui ◽  
Tianmin Xu

Cervical cancer is one of the most common gynecological tumors in females, which is closely related to high-rate HPV infection. Methylation alteration is a type of epigenetic decoration that regulates the expression of genes without changing the DNA sequence, and it is essential for the progression of cervical cancer in pathogenesis while reflecting the prognosis and therapeutic sensitivity in clinical practice. Hydroxymethylation has been discovered in recent years, thus making 5-hmC, the more stable marker, attract more attention in the field of methylation research. As markers of methylation, 5-hmC and 5-mC together with 5-foC and 5-caC draw the outline of the reversible cycle, and 6-mA takes part in the methylation of RNA, especially mRNA. Furthermore, methylation modification participates in ncRNA regulation and histone decoration. In this review, we focus on recent advances in the understanding of methylation regulation in the process of cervical cancer, as well as HPV and CIN, to identify the significant impact on the prospect of overcoming cervical cancer.

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5285 ◽  
Author(s):  
Mei Sze Tan ◽  
Siow-Wee Chang ◽  
Phaik Leng Cheah ◽  
Hwa Jen Yap

Although most of the cervical cancer cases are reported to be closely related to the Human Papillomavirus (HPV) infection, there is a need to study genes that stand up differentially in the final actualization of cervical cancers following HPV infection. In this study, we proposed an integrative machine learning approach to analyse multiple gene expression profiles in cervical cancer in order to identify a set of genetic markers that are associated with and may eventually aid in the diagnosis or prognosis of cervical cancers. The proposed integrative analysis is composed of three steps: namely, (i) gene expression analysis of individual dataset; (ii) meta-analysis of multiple datasets; and (iii) feature selection and machine learning analysis. As a result, 21 gene expressions were identified through the integrative machine learning analysis which including seven supervised and one unsupervised methods. A functional analysis with GSEA (Gene Set Enrichment Analysis) was performed on the selected 21-gene expression set and showed significant enrichment in a nine-potential gene expression signature, namely PEG3, SPON1, BTD and RPLP2 (upregulated genes) and PRDX3, COPB2, LSM3, SLC5A3 and AS1B (downregulated genes).


2020 ◽  
Vol 25 (3) ◽  
pp. 325-331
Author(s):  
Erkan Özmen ◽  
Ülkü Altoparlak ◽  
Muhammet Hamidullah Uyanık ◽  
Abdulkadir Gülen

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.


2018 ◽  
Author(s):  
Sa Do Kang ◽  
Sreejata Chatterjee ◽  
Samina Alam ◽  
Anna C. Salzberg ◽  
Janice Milici ◽  
...  

AbstractHuman papillomavirus (HPV) infection is the world’s most common sexually transmitted infection, and is responsible for most cases of cervical cancer. Previous studies of global gene expression changes induced by HPV infection have focused on the cancerous stages of infection, and therefore, not much is known about global gene expression changes at early pre-neoplastic stages of infection. We show for the first time, global gene expression changes of early stage HPV16 infection in cervical tissue using 3-dimensional organotypic raft cultures that produce high levels of progeny virions.cDNA microarray analysis showed that a total of 594 genes were upregulated and 651 genes were downregulated at least 1.5-fold with HPV16 infection. Gene ontology analysis showed that biological processes including cell cycle progression and DNA metabolism were upregulated, while skin development, immune response, and cell death were downregulated with HPV16 infection in cervical keratinocytes. Individual genes were selected for validation at the transcriptional and translational levels including UBC, which was central to the protein association network of immune response genes, and top downregulated genes RPTN, SERPINB4, KRT23, and KLK8. In particular, KLK8 and SERPINB4 have shown to be upregulated in cancer, which contrasts our results.Organotypic raft cultures that allow full progression of the HPV life-cycle have allowed us to identify novel gene modulations and potential therapeutic targets of early stage HPV infection in cervical tissue. Additionally, our results suggest that early stage productive infection and cancerous stages of infection are distinct disease states expressing different transcriptomes.ImportancePersistent HPV infection is responsible for most cases of cervical cancer. Transition from precancerous to cancerous stages of HPV infection is marked by a significant reduction in virus production. Most global gene expression studies of HPV infection have focused on the cancerous stages. Therefore, little is known about global gene expression changes at precancerous stages. For the first time, we measured global gene expression changes at precancerous stages of HPV16 infection in human cervical tissue producing high levels of virus. We identified a group of genes that are typically overexpressed in cancerous stages to be significantly downregulated at the precancerous stage. Moreover, we identified significantly modulated genes that have not yet been studied in the context of HPV infection. Studying the role of these genes in HPV infection will help us understand what drives the transition from precancerous to cancerous stages, and may lead to development of new therapeutic targets.


2020 ◽  
Author(s):  
Yilun Zhang ◽  
Xin Zhou ◽  
Xiaodong Cai

AbstractIt is known that cis-acting DNA motifs play an important role in regulating gene expression. The genome in a cell thus contains the information that not only encodes for the synthesis of proteins but also is necessary for regulating expression of genes. Therefore, the mRNA level of a gene may be predictable from the DNA sequence. Indeed, three deep neural network models were developed recently to predict the mRNA level of a gene directly or indirectly from the DNA sequence around the transcription start side of the gene. In this work, we develop a deep residual network model, named ExpResNet, to predict gene expression directly from DNA sequence. Applying ExpResNet to the GTEx data, we demonstrate that ExpResNet outperforms the three existing models across four tissues tested. Our model may be useful in the investigation of gene regulation.


2008 ◽  
Vol 26 (10) ◽  
pp. 1037-1043 ◽  
Author(s):  
Victor H. Bermúdez-Morales ◽  
Lourdes X. Gutiérrez ◽  
Juan M. Alcocer-González ◽  
Ana Burguete ◽  
Vicente Madrid-Marina

2020 ◽  
Vol 96 (6) ◽  
pp. 408-410
Author(s):  
Isabela Nemesio ◽  
Fernanda Cury ◽  
Adhemar Longatto-Filho ◽  
José Humberto Fregnani ◽  
Laura Musselwhite ◽  
...  

ObjectivesThe objective of this study was to evaluate the frequency of human papillomavirus (HPV) in the oral cavity of women with and without abnormal cervical cytology and to determine whether there is an association of oral HPV infection with infection of the cervix or with cervical cancer precursor lesions.MethodsThe present study was conducted among 406 women, aged 18–82 years, who attended the Prevention Department of Barretos Cancer Hospital (HCB), Brazil due to a previous altered cervical cytology result. Oral rinse, cervical cytology and biopsy were collected at the same day. The participants also answered a questionnaire about socioeconomic characteristics and risk factors for cervical cancer. Molecular screening for HPV16, HPV18 and 12 other high-risk HPV types was performed on cervical and oral rinse specimens using Cobas 4800 (Roche Molecular Systems, USA).ResultsHPV was detected in the oral rinse of 3.9% of participants. Infection of the oral cavity with a non-HPV16 or 18 type was most frequent (81.2%), followed by HPV16 (18.7%). Infection with HPV in the cervix and oral cavity was present in 11 (2.7%) of participants. There were no differences observed in the smoking status (p value 0.62), mean age of first sexual intercourse (p value 0.25), mean age of the first oral sex (p value 0.90) or mean lifetime number of sexual partners (p value 0.08) between the participants with oral HPV infection or not.ConclusionThe presence of HPV infection in the oral cavity was low in the group of women with abnormal cervical cancer screening findings and a high rate of cervical HPV infection.


Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3513
Author(s):  
Gislaine Curty ◽  
Albert N. Menezes ◽  
Ayslan C. Brant ◽  
Miguel de Mulder Rougvie ◽  
Miguel Ângelo M. Moreira ◽  
...  

Retroelements are expressed in diverse types of cancer and are related to tumorigenesis and to cancer progression. We characterized the expression of retroelements in cervical cancer and explored their interplay with HPV infection and their association with expression of neighboring genes. Forty biopsies of invasive cervical carcinoma (squamous cell carcinomas and adenocarcinomas) with genotyped HPV were selected and analyzed for human endogenous retrovirus (HERV) and long interspersed nuclear element 1 (L1) expression through RNA-seq data. We found 8060 retroelements expressed in the samples and a negative correlation of DNA methyltransferase 1 expression with the two most expressed L1 elements. A total of 103 retroelements were found differentially expressed between tumor histological types and between HPV types, including several HERV families (HERV-K, HERV-H, HERV-E, HERV-I and HERV-L). The comparison between HPV mono- and co-infections showed the highest proportion of differentially expressed L1 elements. The location of retroelements affected neighboring gene expression, such as shown for the interleukin-20 gene family. Three HERVs and seven L1 were located close to this gene family and two L1 showed a positive association with IL20RB expression. This study describes the expression of retroelements in cervical cancer and shows their association with HPV status and host gene expression.


mSphere ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Daniela Vargas-Robles ◽  
Magda Magris ◽  
Natalia Morales ◽  
Maurits N. C. de Koning ◽  
Iveth Rodríguez ◽  
...  

ABSTRACTHuman papillomavirus (HPV), an etiological agent of cervical cancer (CC), has infected humans since ancient times. Amerindians are the furthest migrants out of Africa, and they reached the Americas more than 14,000 years ago. Some groups still remain isolated, and some migrate to towns, forming a gradient spanning urbanization. We hypothesized that, by virtue of their history, lifestyle, and isolation from the global society, remote Amerindian women have lower HPV diversity than do urban women (Amerindian or mestizo). Here we determined the diversity of the 25 most relevant cervical HPV types in 82 Amerindians spanning urbanization (low, medium, and high, consistent with the exposure to urban lifestyles of the town of Puerto Ayacucho in the Venezuelan Amazonas State), and in 29 urban mestizos from the town. Cervical, anal, oral, and introitus samples were taken, and HPVs were typed using reverse DNA hybridization. A total of 23 HPV types were detected, including 11 oncogenic or high-risk types, most associated with CC. Cervical HPV prevalence was 75%, with no differences by group, but Amerindians from low and medium urbanization level had significantly lower HPV diversity than mestizos did. In Amerindians, but not in mestizos, infections by only high-risk HPVs were higher than coinfections or by exclusively low-risk HPVs. Cervical abnormalities only were observed in Amerindians (9/82), consistent with their high HPV infection. The lower cervical HPV diversity in more isolated Amerindians is consistent with their lower exposure to the global pool, and transculturation to urban lifestyles could have implications on HPV ecology, infection, and virulence.IMPORTANCEThe role of HPV type distribution on the disparity of cervical cancer (CC) incidence between human populations remains unknown. The incidence of CC in the Amazonas State of Venezuela is higher than the national average. In this study, we determined the diversity of known HPV types (the viral agent of CC) in Amerindian and mestizo women living in the Venezuelan Amazonas State. Understanding the ecological diversity of HPV in populations undergoing lifestyle transformations has important implication on public health measures for CC prevention.


2021 ◽  
Author(s):  
Sofia L. Alcaraz-Estrada ◽  
Nicolás Serafín-Higuera ◽  
Roberto Ramos-Mondragón ◽  
Octavio D. Reyes-Hernández ◽  
Gabriela Figueroa-González ◽  
...  

Abstract During the different stages of cervical carcinogenesis there is an accumulation of epigenetic alterations leading to changes in gene expression. High-risk human papillomavirus (hrHPV) is a primary risk factor for cervical cancer (CC). Impaired proteolytic processing of histone H3 constitutes a potential epigenetic mechanism in CC. However, whether this event occurs in early stages of the HPV infection is unknown. Using human cervical samples with normal pathology but positive and negative to hrHPV, we identified that the H3 cleavage was low in the hrHPV positive cervix compared to the hrHPV negative cervix. These results suggest that low H3 processing previously observed in CC may be a primary effect of hrHPV infection.


2018 ◽  
Vol 92 (20) ◽  
Author(s):  
Sa Do Kang ◽  
Sreejata Chatterjee ◽  
Samina Alam ◽  
Anna C. Salzberg ◽  
Janice Milici ◽  
...  

ABSTRACTHuman papillomavirus (HPV) infection is the world's most common sexually transmitted infection and is responsible for most cases of cervical cancer. Previous studies of global gene expression changes induced by HPV infection have focused on the cancerous stages of infection, and therefore, not much is known about global gene expression changes at early preneoplastic stages of infection. We show for the first time the global gene expression changes during early-stage HPV16 infection in cervical tissue using 3-dimensional organotypic raft cultures, which produce high levels of progeny virions. cDNA microarray analysis showed that a total of 594 genes were upregulated and 651 genes were downregulated at least 1.5-fold with HPV16 infection. Gene ontology analysis showed that biological processes including cell cycle progression and DNA metabolism were upregulated, while skin development, immune response, and cell death were downregulated with HPV16 infection in cervical keratinocytes. Individual genes were selected for validation at the transcriptional and translational levels, includingUBC, which was central to the protein association network of immune response genes, and top downregulated genesRPTN,SERPINB4,KRT23, andKLK8. In particular,KLK8andSERPINB4were shown to be upregulated in cancer, which contrasts with the gene regulation during the productive replication stage. Organotypic raft cultures, which allow full progression of the HPV life cycle, allowed us to identify novel gene modulations and potential therapeutic targets of early-stage HPV infection in cervical tissue. Additionally, our results suggest that early-stage productive infection and cancerous stages of infection are distinct disease states expressing different host transcriptomes.IMPORTANCEPersistent HPV infection is responsible for most cases of cervical cancer. The transition from precancerous to cancerous stages of HPV infection is marked by a significant reduction in virus production. Most global gene expression studies of HPV infection have focused on the cancerous stages. Therefore, little is known about global gene expression changes at precancerous stages. For the first time, we measured global gene expression changes at the precancerous stages of HPV16 infection in human cervical tissue producing high levels of virus. We identified a group of genes that are typically overexpressed in cancerous stages to be significantly downregulated at the precancerous stage. Moreover, we identified significantly modulated genes that have not yet been studied in the context of HPV infection. Studying the role of these genes in HPV infection will help us understand what drives the transition from precancerous to cancerous stages and may lead to the development of new therapeutic targets.


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