scholarly journals Correction: The application of CRISPR/Cas9 system in cervical carcinogenesis

2021 ◽  
Author(s):  
Chun Gao ◽  
Ping Wu ◽  
Lan Yu ◽  
Liting Liu ◽  
Hong Liu ◽  
...  
Keyword(s):  
Cervical Carcinogenesis

The role of programmed cell death ligand-1/ programmed cell death-1 (PD-L1/PD-1) in HPV-induced cervical cancer and potential for their use in blockade therapy

2020 ◽  
Vol 27 ◽  
Author(s):  
Lifang Zhang ◽  
Yu Zhao ◽  
Quanmei Tu ◽  
Xiangyang Xue ◽  
Xueqiong Zhu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Escape ◽  
Hypoxia Inducible Factor ◽  
Hpv Infection ◽  
Advanced Cervical Cancer ◽  
Cervical Carcinogenesis ◽  
Programmed Cell Death 1

Background: Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months. Methods: We undertook a structural search of peer-reviewed published studies based on 1). Characteristics of programmed cell death ligand-1/programmed cell death-1(PD-L1/PD-1) expression in cervical cancer and upstream regulatory signals of PD-L1/PD-1 expression, 2). The role of the PD-L1/PD-1 axis in cervical carcinogenesis induced by HPV infection and 3). Whether the PD-L1/PD-1 axis has emerged as a potential target for cervical cancer therapies. Results: One hundred and twenty-six published papers were included in the review, demonstrating that expression of PD-L1/PD-1 is associated with HPV-caused cancer, especially with HPV 16 and 18 which account for approximately 70% of cervical cancer cases. HPV E5/E6/E7 oncogenes activate multiple signaling pathways including PI3K/AKT, MAPK, hypoxia-inducible factor 1α, STAT3/NF-kB and MicroRNAs, which regulate PD-L1/PD-1 axis to promote HPV-induced cervical carcinogenesis. The PD-L1/PD-1 axis plays a crucial role in immune escape of cervical cancer through inhibition of host immune response. creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance, which provides a rationale for therapeutic blockade of this axis in HPV-positive cancers. Currently, Phase I/II clinical trials evaluating the effects of PD-L1/PD-1 targeted therapies are in progress for cervical carcinoma, which provide an important opportunity for the application of anti-PD-L1/anti-PD-1 antibodies in cervical cancer treatment. Conclusion: Recent research developments have led to an entirely new class of drugs using antibodies against the PD-L1/PD-1 thus promoting the body’s immune system to fight the cancer. The expression and roles of the PD-L1/ PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted cancer therapy.

scholarly journals Competing Endogenous RNAs in Cervical Carcinogenesis: A New Layer of Complexity

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 991
Author(s):  
Fernanda Costa Brandão Berti ◽  
Sara Cristina Lobo-Alves ◽  
Camila de Freitas Oliveira-Toré ◽  
Amanda Salviano-Silva ◽  
Karen Brajão de Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fine Tuning ◽  
Molecular Networks ◽  
Cervical Carcinogenesis ◽  
Molecular Changes ◽  
Cellular Processes ◽  
Target Mrnas ◽  
Competing Endogenous Rnas ◽  
Cervical Cells ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs) regulate gene expression by binding to complementary sequences within target mRNAs. Apart from working ‘solo’, miRNAs may interact in important molecular networks such as competing endogenous RNA (ceRNA) axes. By competing for a limited pool of miRNAs, transcripts such as long noncoding RNAs (lncRNAs) and mRNAs can regulate each other, fine-tuning gene expression. Several ceRNA networks led by different lncRNAs—described here as lncRNA-mediated ceRNAs—seem to play essential roles in cervical cancer (CC). By conducting an extensive search, we summarized networks involved in CC, highlighting the major impacts of such dynamic molecular changes over multiple cellular processes. Through the sponging of distinct miRNAs, some lncRNAs as HOTAIR, MALAT1, NEAT1, OIP5-AS1, and XIST trigger crucial molecular changes, ultimately increasing cell proliferation, migration, invasion, and inhibiting apoptosis. Likewise, several lncRNAs seem to be a sponge for important tumor-suppressive miRNAs (as miR-140-5p, miR-143-3p, miR-148a-3p, and miR-206), impairing such molecules from exerting a negative post-transcriptional regulation over target mRNAs. Curiously, some of the involved mRNAs code for important proteins such as PTEN, ROCK1, and MAPK1, known to modulate cell growth, proliferation, apoptosis, and adhesion in CC. Overall, we highlight important lncRNA-mediated functional interactions occurring in cervical cells and their closely related impact on cervical carcinogenesis.

scholarly journals Association of cervical carcinogenesis risk with HPV16 E6 and E7 variants in the Taizhou area, China

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mei-Zhen Dai ◽  
Yi Qiu ◽  
Xing-Hong Di ◽  
Wei-Wu Shi ◽  
Hui-Hui Xu
Keyword(s):  
Cervical Cancer ◽  
Cervical Carcinogenesis ◽  
Chi Square ◽  
Major Health Problem ◽  
Hpv16 E6 ◽  
Exact Test ◽  
Chi Square Test ◽  
E6 And E7

Abstract Background Human papillomavirus (HPV) type 16 accounts for a larger share of cervical cancer and has been a major health problem worldwide for decades. The progression of initial infection to cervical cancer has been linked to viral sequence properties; however, the role of HPV16 variants in the risk of cervical carcinogenesis, especially with longitudinal follow-up, is not fully understood in China. Methods We aimed to investigate the genetic variability of HPV16 E6 and E7 oncogenes in isolates from cervical exfoliated cells. Between December 2012 and December 2014, a total of 310 single HPV16-positive samples were selected from women living in the Taizhou area, China. Sequences of all E6 and E7 oncogenes were analysed by PCR-sequencing assay. Detailed sequence comparison, genetic heterogeneity analyses and maximum-likelihood phylogenetic tree construction were performed with BioEdit Sequence Alignment Editor and MEGA X software. Data for cytology tests and histological diagnoses were obtained from our Taizhou Area Study with longitudinal follow-up for at least 5 years. The relationship between HPV16 variants and cervical carcinogenesis risk was analysed by the chi-square test or Fisher’s exact test. Results In this study, we obtained 64 distinct variation patterns with the accession GenBank numbers MT681266-MT681329. Phylogenetic analysis revealed that 98.3% of HPV16 variants belong to lineage A, in which the A4 (Asian) sublineage was dominant (64.8%), followed by A2 (12.1%), A1 (11.4%), and A3 (10.0%). The A4 (Asian) sublineage had a higher risk of CIN2+ than the A1–3 (European) sublineages (OR = 2.69, 95% CI = 1.04–6.97, P < 0.05). Furthermore, nucleotide variation in HPV16 E6 T178G is associated with the development of cervical cancer. Conclusion These data could provide novel insights into the role of HPV16 variants in cervical carcinogenesis risk in China.

scholarly journals The application of CRISPR/Cas9 system in cervical carcinogenesis

2021 ◽  
Author(s):  
Chun Gao ◽  
Ping Wu ◽  
Lan Yu ◽  
Liting Liu ◽  
Hong Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Transgenic Mice ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Precancerous Lesions ◽  
Cancer Cell Lines ◽  
Cervical Carcinogenesis ◽  
Cervical Precancerous Lesions

AbstractIntegration of high-risk HPV genomes into cellular chromatin has been confirmed to promote cervical carcinogenesis, with HPV16 being the most prevalent high-risk type. Herein, we evaluated the therapeutic effect of the CRISPR/Cas9 system in cervical carcinogenesis, especially for cervical precancerous lesions. In cervical cancer/pre-cancer cell lines, we transfected the HPV16 E7 targeted CRISPR/Cas9, TALEN, ZFN plasmids, respectively. Compared to previous established ZFN and TALEN systems, CRISPR/Cas9 has shown comparable efficiency and specificity in inhibiting cell growth and colony formation and inducing apoptosis in cervical cancer/pre-cancer cell lines, which seemed to be more pronounced in the S12 cell line derived from the low-grade cervical lesion. Furthermore, in xenograft formation assays, CRISPR/Cas9 inhibited tumor formation of the S12 cell line in vivo and affected the corresponding protein expression. In the K14-HPV16 transgenic mice model of HPV-driven spontaneous cervical carcinogenesis, cervical application of CRISPR/Cas9 treatment caused mutations of the E7 gene and restored the expression of RB, E2F1, and CDK2, thereby reversing the cervical carcinogenesis phenotype. In this study, we have demonstrated that CRISPR/Cas9 targeting HPV16 E7 could effectively revert the HPV-related cervical carcinogenesis in vitro, as well as in K14-HPV16 transgenic mice, which has shown great potential in clinical treatment for cervical precancerous lesions.

Epstein-Barr virus plays little role in cervical carcinogenesis in Korean women

2005 ◽  
Vol 15 (2) ◽  
pp. 312-318 ◽  
Author(s):  
S.S. Seo ◽  
W.H. Kim ◽  
Y.S. Song ◽  
S.H. Kim ◽  
J.W. Kim ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Cervical Carcinogenesis ◽  
Korean Women ◽  
Barr Virus ◽  
Epstein Barr

COX-2 overexpression as a biomarker of early cervical carcinogenesis: A pilot study

2007 ◽  
Vol 107 (1) ◽  
pp. S155-S162 ◽  
Author(s):  
J. Salvador Saldivar ◽  
David Lopez ◽  
Rebecca A. Feldman ◽  
Reena Tharappel-Jacob ◽  
Antonio de la Rosa ◽  
...  
Keyword(s):  
Pilot Study ◽  
Cervical Carcinogenesis ◽  
Cox 2

scholarly journals Depletion of HPV16 early genes induces autophagy and senescence in a cervical carcinogenesis model, regardless of viral physical state

2013 ◽  
Vol 231 (3) ◽  
pp. 354-366 ◽  
Author(s):  
Jennifer E Hanning ◽  
Harpreet K Saini ◽  
Matthew J Murray ◽  
Maria M Caffarel ◽  
Stijn van Dongen ◽  
...  
Keyword(s):  
Physical State ◽  
Cervical Carcinogenesis ◽  
Early Genes

scholarly journals Genetic Polymorphism of Cancer Susceptibility Genes and HPV Infection in Cervical Carcinogenesis

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Osamu Nunobiki ◽  
Masatsugu Ueda ◽  
Eisaku Toji ◽  
Michiko Yamamoto ◽  
Kyoko Akashi ◽  
...  
Keyword(s):  
Cancer Susceptibility ◽  
Association Studies ◽  
Gene Promoter ◽  
Hpv Infection ◽  
Host Susceptibility ◽  
Cervical Carcinogenesis ◽  
Mdm2 Gene ◽  
P53 Codon 72 ◽  
Cancer Susceptibility Genes ◽  
Hpv Types

It is widely accepted that specific human papillomavirus (HPV) types are the central etiologic agent of cervical carcinogenesis. However, a number of infected women do not develop invasive lesions, suggesting that other environmental and host factors may play decisive roles in the persistence of HPV infection and further malignant conversion of cervical epithelium. Although many previous reports have focused on HPV and environmental factors, the role of host susceptibility to cervical carcinogenesis is largely unknown. Here, we review the findings of genetic association studies in cervical carcinogenesis with special reference to polymorphisms of glutathione-S-transferase (GST) isoforms, p53 codon 72, murine double-minute 2 homolog (MDM2) gene promoter 309, and FAS gene promoter -670 together with HPV types including our recent research results.

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