Deregulation of miR-21 and miR-29a in Cervical Cancer Related to HPV Infection

MicroRNA ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 110-115 ◽  
Author(s):  
Sara Zamani ◽  
Amir Sohrabi ◽  
Seyed Masoud Hosseini ◽  
Marjan Rahnamaye-Farzami ◽  
Abolfazl Akbari

Background:Early diagnosis is an important factor to improve the survival of Invasive Cervical Cancer (ICC) patients. Molecular biomarkers such as micro RNA (miRNA) can be used in the early detection of ICC. The expression of miR-21 and miR-29a are deregulated in many types of human cancers.Objective:The aim of this study was to investigate the differences in miR-21 and miR-29a expression patterns in the Human Papilloma Virus (HPV) infection and various grades of cervical cancer among Iranian women.Methods:Small RNAs were extracted from positive for HPV, cervical cancer and healthy samples from 43, 50 and 46 individuals, respectively. Expression levels of miR-21 and miR-29a were analyzed by SYBR Green real-time RT-PCR using specific primers, and 5s rRNA as the internal reference gene.Results:Results have shown a significant increase in miR-21 and decrease in miR-29 in cancerous samples in comparison with the control groups (P < 0.0001).Conclusion:This study illustrated that miR-21 and miR-29a could be operated as an oncogene and tumor-suppressor in cervical cancer progression. More studies are needed to demonstrate the role of miR-21 and miR-29a as potential biomarkers for the diagnosis of cervical cancer in future investigations.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yang Liu ◽  
Pianping Fan ◽  
Yingying Yang ◽  
Changjun Xu ◽  
Yajuan Huang ◽  
...  

Abstract This study aimed to examine hTERC gene in different grades of cervical intraepithelial neoplasia (CIN) and cervical cancer, and the association between hTERC and high risk-human papillomavirus (HR-HPV) infection. Patients who underwent cervical cancer screening at the Second Affiliated Hospital of Kunming Medical University between October 2010 and December 2011 were enrolled. All patients underwent liquid-based cytology test and hybrid capture 2 (HC2) for HPV detection. hTERC was examined using fluorescence in situ hybridization (FISH). Cervical colposcopy biopsy was performed if any of the three results was positive. HC2, FISH, and pathology were compared. A total of 1200 women underwent screening, 150 patients underwent cervical biopsy: 32 in the normal group, 38 in the CIN1 group, 66 in the CIN2/3 group, and 14 in the invasive cervical cancer group. More patients had HR-HPV infection in the CIN2/3 group and ICC group compared with the CIN1 group. hTERC increased with increasing histological dysplasia. There was significant difference in hTERC positive rate between each of the three groups. More patients with hTERC gene amplification were observed in the positive HR-HPV group than in the HR-HPV negative group. In conclusion, hTERC is a potential marker for precancerous cervical cancer lesions. hTERC might be correlated with HR-HPV infection in cervical diseases.


MicroRNA ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Carolina R. Hoelzle ◽  
Solène Arnoult ◽  
Cinthya R.M. Borém ◽  
Mariana Ottone ◽  
Kênia C.S.F. de Magalhães ◽  
...  

Background: miR-21, miR-214, and miR-let-7a are three validated and well-known miRNAs. miR-21 is described as an “oncomir,” while miR-214 and miR-let-7a are described mainly as tumor suppressors. The role of these miRNAs remains unclear in cervical cancer, an important malignancy among women worldwide and responsible for many deaths every year. Objective: The objective of this study was to describe the expression profile of miR-21, miR-214, and miR-let-7a in plasma and cervical scraping from a control group and patients with different grades of cervical lesions and invasive cervical cancer, and then correlate with HPV infection groups. Methods: Plasma and cervical scraping were submitted to DNA and RNA extraction. HPV detection and typing were performed by conventional PCR followed by PAGE to amplicons interpretation. The miRNA relative expression in plasma and cervical scraping samples was performed by real-time PCR using specific TaqMan probes. Results: miR-21 (p=0.0277) and miR-214 (p=0.0151) were up-regulated in cervical scraping samples of the invasive cervical cancer (ICC) group. However, miR-214 was also up-regulated in the LSIL group (p=0.0062). Both miRNAs were not related to HPV infection. However, miR-let-7a was higher in HPV positive plasma samples (p=0.0433) than in HPV negative plasma samples, and the correlation analysis confirmed the association between the levels of this miRNA with the presence of HPV (p=0.0407; r=0.3029), but not with lesion grade (p>0.05). Conclusion: Our results suggest that miR-21 is related to cervical cancer progression and miR-214 appears to have an ambiguous role in cervical lesions. miR-let-7a may be upregulated at the systemic level in patients with HPV infection.


2018 ◽  
Vol 2 (2) ◽  
pp. 81-87
Author(s):  
Agnes S. Rahayu

Human papillomavirus (HPV) is a significant source of morbidity and mortality worldwide. The primary risk factors for aquiring HPV are generally associated with sexual activity.  Evidence suggest that condoms provide some protection against infection and disease progression, but any genital contact is sufficient for HPV transmission.  Having more than one sexual partner often result in HPV infection.  All sexually active adolescents are at high risk for aquiring HPV.  Persistent infection with high-risk HPV types (e.g HPV 16 or 18) is considered necessary for the development cervical cancer.  Most infection are asymptomatic and are efficiently cleared by he immune system.  The lesions that caused by HPV can regress in adolescent and young adult women.  A small percentage of adolescents will develop precancerous lesions that may progress to invasive cervical cancer.  Adolescents should be given appropriate education about HPV and the dangers associated with infection.  Vaccination for HPV infection should be given for presexually active children and adolescents.Key words: human papilloma virus, adolescent, cervical cancer, vaccination. 


Author(s):  
Travis T. Sims ◽  
Lauren E. Colbert ◽  
Ann H. Klopp

ABSTRACT The microbiome, which refers to the microbiota within a host and their collective genomes, has recently been demonstrated to play a critical role in cancer progression, metastasis, and therapeutic response. The microbiome is known to affect host immunity, but its influence on human papilloma virus (HPV) gynecologic malignancies remains limited and poorly understood. To date, studies have largely focused on the cervicovaginal microbiome; however, there is growing evidence that the gut microbiome may interact and substantially affect therapeutic response in gynecologic cancers. Importantly, new developments in microbiome sequencing and advanced bioinformatics technologies have enabled rapid advances in our understanding of the gut and local tumor microbiota. In this review, we examine the evidence supporting the role of the microbiome in HPV-associated cervical intraepithelial neoplasia (CIN) and cervical cancer, explore characteristics that influence and shape the host microbiota that impact HPV-driven carcinogenesis, and highlight potential approaches and considerations for future and ongoing research of the microbiome's effect on HPV-associated cancer.


2019 ◽  
Vol 21 (1) ◽  
pp. 222 ◽  
Author(s):  
Gislaine Curty ◽  
Pedro S. de Carvalho ◽  
Marcelo A. Soares

The microbiome is able to modulate immune responses, alter the physiology of the human organism, and increase the risk of viral infections and development of diseases such as cancer. In this review, we address changes in the cervical microbiota as potential biomarkers to identify the risk of cervical intraepithelial neoplasia (CIN) development and invasive cervical cancer in the context of human papillomavirus (HPV) infection. Current approaches for clinical diagnostics and the manipulation of microbiota with the use of probiotics and through microbiota transplantation are also discussed.


Author(s):  
Lifang Zhang ◽  
Yu Zhao ◽  
Quanmei Tu ◽  
Xiangyang Xue ◽  
Xueqiong Zhu ◽  
...  

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.


2018 ◽  
Vol 19 (9) ◽  
pp. 798-805 ◽  
Author(s):  
Mohd Saeed ◽  
Fawaz D. Alshammari ◽  
Md. Jahoor Alam ◽  
Khan Mohd Sarim ◽  
Khurshid Ahmad ◽  
...  

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stanie Gaete ◽  
Aviane Auguste ◽  
Bernard Bhakkan ◽  
Jessica Peruvien ◽  
Cecile Herrmann-Storck ◽  
...  

Abstract Background Cervical cancer is the fourth cancer worldwide. The Human Papilloma Virus is responsible for 99% of the cases but the distribution of its genotypes varies among populations. We aimed to identify HPV genotypes distribution in women with grade 2/3 cervical intraepithelial dysplasia or invasive cervical cancer in Guadeloupe, a French Caribbean territory with a population mainly of African descent. Methods We used paraffin-embedded tumors for viral DNA extraction from women diagnosed between 2014 and 2016 and identified by the population-based cancer registry. The HPV Genotyping was performed with the InnoLIPA HPV Genotyping Extra kit®. Results Overall, 213 samples out of the 321 eligible records were analyzed. The HPV status was positive for 94% of the cases. The five most common oncogenic HPV genotypes were HPV31 (47%), HPV33 (38%), HPV16 (32%), HPV44 (31%) and HPV26 (28%). HPV18 was found in only in 5% of the cases. Among the studied cases, 94% had multiple infections. More than 60% of single infections were HPV16-related, accounting for 35% of HPV16 infections. Conclusions These results show a different distribution of oncogenic HPVs in Guadeloupe with “31 >  33 > 16” and a high frequency of multiple infections. Despite a lower coverage, the nine-valent vaccine is nevertheless adequate.


2021 ◽  
Vol 16 (1) ◽  
pp. 1-13
Author(s):  
Weiwei Liu ◽  
Dongmei Yao ◽  
Bo Huang

Abstract Cervical cancer (CC) is a huge threat to the health of women worldwide. Long non-coding RNA plasmacytoma variant translocation 1 gene (PVT1) was proved to be associated with the development of diverse human cancers, including CC. Nevertheless, the exact mechanism of PVT1 in CC progression remains unclear. Levels of PVT1, microRNA-503 (miR-503), and ADP ribosylation factor-like protein 2 (ARL2) were measured by quantitative reverse transcription-polymerase chain reaction or western blot assay. 3-(4,5)-Dimethylthiazole-2-y1)-2,5-biphenyl tetrazolium bromide (MTT) and flow cytometry were used to examine cell viability and apoptosis, respectively. For migration and invasion detection, transwell assay was performed. The interaction between miR-503 and PVT1 or ARL2 was shown by dual luciferase reporter assay. A nude mouse model was constructed to clarify the role of PVT1 in vivo. PVT1 and ARL2 expressions were increased, whereas miR-503 expression was decreased in CC tissues and cells. PVT1 was a sponge of miR-503, and miR-503 targeted ARL2. PVT1 knockdown suppressed proliferation, migration, and invasion of CC cells, which could be largely reverted by miR-503 inhibitor. In addition, upregulated ARL2 could attenuate si-PVT1-mediated anti-proliferation and anti-metastasis effects on CC cells. Silenced PVT1 also inhibited CC tumor growth in vivo. PVT1 knockdown exerted tumor suppressor role in CC progression via the miR-503/ARL2 axis, at least in part.


Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2089
Author(s):  
Simona Duranti ◽  
Antonella Pietragalla ◽  
Gennaro Daniele ◽  
Camilla Nero ◽  
Francesca Ciccarone ◽  
...  

Human papillomavirus (HPV) infection is the recognized cause of almost all cervical cancers. Despite the reduction in incidence due to a wide use of screening programs and a specific vaccine, the prognosis of cervical cancer remains poor, especially for late-stage and relapsed disease. Considering the elevated rates of PD-L1 expression in up to 80% of cervical cancers, a strong rationale supports the use of immunotherapy to restore the immune response against tumor. The aim of this review is to analyze the possible role of immune checkpoint inhibitors in cervical cancer treatment, with a particular focus on the rationale and on the results of phase I and II clinical trials. An overview of ongoing phase III studies with possible future areas of development is also provided.


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