Human papillomavirus types 16 E1 mRNA is transcribed from P14 early promoter in cervical neoplasms

Fedorova, M. D.; Vinokurova, Svetlana; Павлова, Л. С.; Komel'kov, Andrei; Короленкова, Л. И.; Kisseljov, F. L.; Kisseljova, N. P.

doi:10.1016/j.virol.2015.11.015

Cited by 7 publications

(6 citation statements)

References 17 publications

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“…In advanced CC, metastases can be present out of pelvic to distant organs, such as lungs [5]. Although persistent infection of high-risk human papillomavirus (HPV) is confirmed to be associated with the development of the majority of CC [9, 10], the molecular mechanism underlying cervical carcinogenesis and tumor progression remain unclear and there has been no accurate biomarker for predicting aggressiveness and prognosis of CC so far. [11].…”

Section: Introductionmentioning

confidence: 99%

Tripartite motif containing 62 is a novel prognostic marker and suppresses tumor metastasis via c-Jun/Slug signaling-mediated epithelial-mesenchymal transition in cervical cancer

Chen

Shang

et al. 2016

J Exp Clin Cancer Res

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BackgroundTRIM62 (tripartite motif containing 62) has been found to act as a tumor suppressor of several cancers. However, its precise biological role and related mechanism remain unknown in cervical cancer (CC).MethodsQuantitative Real-time PCR and western blot were adopted to detect the mRNA and protein expression level of TRIM62 in both human CC cell lines and tissues. Immunohistochemistry was used to measure the TRIM62 expression in 30 normal cervical and 189 CC tissues. Univariate and multivariate Cox regression analyses and Kaplan–Meier survival analyses performed to investigate the association between TRIM62 expression and CC patients’ prognosis. The effect of TRIM62 on CC growth and metastasis was studied in vitro and in vivo. Multi-pathway reporter array were utilized to identify the potential signaling manipulated by TRIM62.ResultsTRIM62 was frequently down-regulated in both human CC cells and tissues. Low expression of TRIM62 in CC tissues was associated with aggressive clinicopathological features of CC patients. In addition, TRIM62 was also an independent poor prognostic factor for overall and disease-free survival of CC patients after surgery. Moreover, enforced expression of TRIM62 in CC cells significantly inhibited their abilities of proliferation, migration and invasion in vitro. Besides, subcutaneous xenograft tumor model and xenograft mouse metastatic model respectively displayed that TRIM62 impeded the growth and metastasis of CC in vivo. Furthermore, mechanism study exhibited that TRIM62 could suppress epithelial-mesenchymal transition (EMT) by inhibiting c-Jun/Slug signaling. The inhibitory role of TRIM62 in tumor proliferation might be through regulating cell cycle related proteins CyclinD1 and P27 by targeting c-Jun.ConclusionTRIM62 is a potential prognostic biomarker in CC and suppresses metastasis of CC via inhibiting c-Jun/Slug signaling-mediated EMT.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0445-5) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Tripartite motif containing 62 is a novel prognostic marker and suppresses tumor metastasis via c-Jun/Slug signaling-mediated epithelial-mesenchymal transition in cervical cancer

Chen

Shang

et al. 2016

J Exp Clin Cancer Res

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“…A recent study discovered p14, a novel promoter for HPV16 E1. It would be interesting to study the E1 expression pattern of this novel promotor in normal and CIN 1 samples in addition to the CIN 2-positive samples as previously described [40]. In addition, the lack of a proper E1 antibody was a limiting factor in investigating E1 protein expression in different clinical stages.…”

Section: Discussionmentioning

confidence: 99%

Elevated HPV16 E1 Expression Is Associated with Cervical Cancer Progression

2017

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Objectives: The primary replication protein, HPV E1, has been shown to play a role in mitigating host defence and disrupting normal cell cycle processes, leading to the development of cancer. This study investigated the expression profile of HPV16 E1 in various stages of cervical cancer development and the factors that control E1 expression. Methods: One hundred and twenty-four HPV16-positive cervical samples ranging from normal to CIN 1, CIN 2/3, and SCC lesions were studied. E1 mRNA expression was determined by ddPCR. Methylation of promoters p97 and p670 was quantified by pyrosequencing, while PCR, qPCR, and sequencing were used to determine the physical state and variations of the HPV16 E1 genome. Results: Increased E1 mRNA expression related to disease progression (normal 0.18, CIN 1 0.41, CIN 2/3 0.65, and SCC 0.79) was demonstrated with a significant positive correlation (r = 0.661, p = 0.019). No association between physical state and E1 expression was found. Methylation of p97 and p670 promoters showed significant elevation in SCC compared to normal samples. Only 4.2% showed genomic variations of HPV16 E1 63-bp duplication. Conclusion: E1 may play a role in cancer development. The detection of E1 mRNA and promoter methylation may be useful as cancer prognostic markers.

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“…On the other hand, E1 could be acting indirectly throughout its interaction with transcriptional regulators. Interestingly, E1 mRNA has been shown to increase with an increasing grade of cervical intraepithelial neoplasia (CIN), with higher levels found in cervical cancer [ 17 , 41 ]. This indicates that E1 could have effects beyond the viral genome amplification and that the inhibition of the immune response could be contributing to the carcinogenic process; however, this possible role of the E1 protein remains to be explored.…”

Section: Deregulation Of the Ifn Pathway By Hpv Proteinsmentioning

confidence: 99%

Alteration of the IFN-Pathway by Human Papillomavirus Proteins: Antiviral Immune Response Evasion Mechanism

et al. 2022

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A persistent infection with the so-called high-risk Human Papillomaviruses (hr-HPVs) plays a fundamental role in the development of different neoplasms. The expression of the HPV proteins throughout the different steps of the viral life cycle produce a disruption of several cellular processes, including immune response, which can lead to cell transformation. The interferon-mediated response plays an important role in eliminating HPV-infected and -transformed cells. The ability of HPV to disrupt the proper function of the interferon response is based on a series of molecular mechanisms coordinated by HPV proteins intended to prevent clearance of infection, ultimately producing an immunotolerant environment that facilitates the establishment of persistence and cancer. In this review, we focus on the molecular actions performed by HPV E1, E2, E5, E6 and E7 proteins on IFN signaling elements and their contribution to the establishment of infection, viral persistence and the progression to cancer.

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Human papillomavirus types 16 E1 mRNA is transcribed from P14 early promoter in cervical neoplasms

Cited by 7 publications

References 17 publications

Tripartite motif containing 62 is a novel prognostic marker and suppresses tumor metastasis via c-Jun/Slug signaling-mediated epithelial-mesenchymal transition in cervical cancer

Tripartite motif containing 62 is a novel prognostic marker and suppresses tumor metastasis via c-Jun/Slug signaling-mediated epithelial-mesenchymal transition in cervical cancer

Elevated HPV16 E1 Expression Is Associated with Cervical Cancer Progression

Alteration of the IFN-Pathway by Human Papillomavirus Proteins: Antiviral Immune Response Evasion Mechanism

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