scholarly journals Extracellular vesicular Wnt7b mediates HPV E6-induced cervical cancer angiogenesis by activating the β-catenin signaling pathway

2020 ◽  
Author(s):  
Jun-Jun Qiu ◽  
Shu-Gen Sun ◽  
Xiao-Yan Tang ◽  
Ying-Ying Lin ◽  
Keqin Hua
Keyword(s):  
Cervical Cancer ◽  
Umbilical Vein ◽  
Predictive Biomarker ◽  
Good Prediction ◽  
Hpv 16 ◽  
Hpv E6 ◽  
In Vivo Experiments ◽  
Cancer Tumor

Abstract Background: The E6 oncoproteins of human papillomavirus (HPV) 16/18 are the critical drivers of cervical cancer (CC) progression. Extracellular vesicles (EVs) are emerging as critical mediators of cancer-tumor microenvironment (TME) communication. However, whether EVs contribute to HPV 16/18 E6-mediated impacts on CC progression remains unclear. Methods: A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of EV-Wnt7b in HPV E6-induced CC angiogenesis. The prognostic value of serum EV-Wnt7b was determined and a predictive nomogram model was established. Results: HPV 16/18 E6 upregulated Wnt7b mRNA expression in four HPV 16/18-positive CC cell lines and their EVs. In vitro and in vivo experiments demonstrated that EV-Wnt7b mRNA was transferred to and modulated human umbilical vein endothelial cells (HUVECs) toward more proliferative and proangiogenic behaviors by impacting β-catenin signaling. Clinically, serum EV-Wnt7b levels were elevated in CC patients and significantly correlated with an aggressive phenotype. Serum EV-Wnt7b was determined to be an independent prognostic factor for CC overall survival (OS) and recurrence-free survival (RFS). Notably, we successfully established a novel predictive nomogram model using serum EV-Wnt7b, which showed good prediction of 1- and 3-year OS and RFS. Conclusions: Our results illustrate a potential crosstalk between HPV 16/18-positive CC cells and HUVECs via EVs in the TME and highlight the potential of circulating EV-Wnt7b as a novel predictive biomarker for CC prognosis.

scholarly journals Extracellular vesicular Wnt7b mediates HPV E6-induced cervical cancer angiogenesis by activating the β-catenin signaling pathway

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Jun-Jun Qiu ◽  
Shu-Gen Sun ◽  
Xiao-Yan Tang ◽  
Ying-Ying Lin ◽  
Ke-Qin Hua
Keyword(s):  
Cervical Cancer ◽  
Umbilical Vein ◽  
Predictive Biomarker ◽  
Good Prediction ◽  
Hpv 16 ◽  
Hpv E6 ◽  
In Vivo Experiments ◽  
Cancer Tumor

Abstract Background The E6 oncoproteins of human papillomavirus (HPV) 16/18 are the critical drivers of cervical cancer (CC) progression. Extracellular vesicles (EVs) are emerging as critical mediators of cancer-tumor microenvironment (TME) communication. However, whether EVs contribute to HPV 16/18 E6-mediated impacts on CC progression remains unclear. Methods A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of EV-Wnt7b in HPV E6-induced CC angiogenesis. The prognostic value of serum EV-Wnt7b was determined and a predictive nomogram model was established. Results HPV 16/18 E6 upregulated Wnt7b mRNA expression in four HPV 16/18-positive CC cell lines and their EVs. In vitro and in vivo experiments demonstrated that EV-Wnt7b mRNA was transferred to and modulated human umbilical vein endothelial cells (HUVECs) toward more proliferative and proangiogenic behaviors by impacting β-catenin signaling. Clinically, serum EV-Wnt7b levels were elevated in CC patients and significantly correlated with an aggressive phenotype. Serum EV-Wnt7b was determined to be an independent prognostic factor for CC overall survival (OS) and recurrence-free survival (RFS). Notably, we successfully established a novel predictive nomogram model using serum EV-Wnt7b, which showed good prediction of 1- and 3-year OS and RFS. Conclusions Our results illustrate a potential crosstalk between HPV 16/18-positive CC cells and HUVECs via EVs in the TME and highlight the potential of circulating EV-Wnt7b as a novel predictive biomarker for CC prognosis.

scholarly journals Extracellular vesicular Wnt7b mediates HPV E6-induced cervical cancer angiogenesis by activating the β-catenin signaling pathway

2020 ◽  
Author(s):  
Jun-Jun Qiu ◽  
Shu-Gen Sun ◽  
Xiao-Yan Tang ◽  
Ying-Ying Lin ◽  
Keqin Hua
Keyword(s):  
Cervical Cancer ◽  
Umbilical Vein ◽  
Predictive Biomarker ◽  
Good Prediction ◽  
Hpv 16 ◽  
Hpv E6 ◽  
In Vivo Experiments ◽  
Cancer Tumor

Abstract Background The E6 oncoproteins of human papillomavirus (HPV) 16/18 are the critical drivers of cervical cancer (CC) progression. Extracellular vesicles (EVs) are emerging as critical mediators of cancer-tumor microenvironment (TME) communication. However, whether EVs contribute to HPV 16/18 E6-mediated impacts on CC progression remains unclear. Methods A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of EV-Wnt7b in HPV E6-induced CC angiogenesis. The prognostic value of serum EV-Wnt7b was determined and a predictive nomogram model was established. Results HPV 16/18 E6 upregulated Wnt7b expression in four HPV 16/18-positive CC cell lines and their EVs. In vitro and in vivo experiments demonstrated that EV-Wnt7b was transferred to and modulated human umbilical vein endothelial cells (HUVECs) toward more proliferative and proangiogenic behaviors by impacting β-catenin signaling. Clinically, serum EV-Wnt7b levels were elevated in CC patients and significantly correlated with an aggressive phenotype. Serum EV-Wnt7b was determined to be an independent prognostic factor for CC overall survival (OS) and recurrence-free survival (RFS). Notably, we successfully established a novel predictive nomogram model using serum EV-Wnt7b, which showed good prediction of 1- and 3-year OS and RFS. Conclusions Our results illustrate a potential crosstalk between HPV 16/18-positive CC cells and HUVECs via EVs in the TME and highlight the potential of circulating EV-Wnt7b as a novel predictive biomarker for CC prognosis.

scholarly journals UBE2C Drives Human Cervical Cancer Progression and Is Positively Modulated by mTOR

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 37
Author(s):  
An-Jen Chiang ◽  
Chia-Jung Li ◽  
Kuan-Hao Tsui ◽  
Chung Chang ◽  
Yuan-chin Ivan Chang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Cancer Staging ◽  
Cervical Squamous Cell Carcinoma ◽  
Cancer Cell Proliferation ◽  
Gynecological Malignancy ◽  
In Vivo Experiments ◽  
Ubiquitin Conjugating Enzyme

Cervical cancer is a common gynecological malignancy, accounting for 10% of all gynecological cancers. Recently, targeted therapy for cervical cancer has shown unprecedented advantages. Several studies have shown that ubiquitin conjugating enzyme E2 (UBE2C) is highly expressed in a series of tumors, and participates in the progression of these tumors. However, the possible impact of UBE2C on the progression of cervical squamous cell carcinoma (CESC) remains unclear. Here, we carried out tissue microarray analysis of paraffin-embedded tissues from 294 cervical cancer patients with FIGO/TNM cancer staging records. The results indicated that UBE2C was highly expressed in human CESC tissues and its expression was related to the clinical characteristics of CESC patients. Overexpression and knockdown of UBE2C enhanced and reduced cervical cancer cell proliferation, respectively, in vitro. Furthermore, in vivo experiments showed that UBE2C regulated the expression and activity of the mTOR/PI3K/AKT pathway. In summary, we confirmed that UBE2C is involved in the process of CESC and that UBE2C may represent a molecular target for CESC treatment.

scholarly journals Design of a multi-epitope vaccine against cervical cancer using immunoinformatics approaches

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samira Sanami ◽  
Fatemeh Azadegan-Dehkordi ◽  
Mahmoud Rafieian-Kopaei ◽  
Majid Salehi ◽  
Maryam Ghasemi-Dehnoo ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
T Lymphocytes ◽  
Tertiary Structure ◽  
Therapeutic Vaccine ◽  
Epitope Prediction ◽  
Therapeutic Effects ◽  
Epitope Vaccine ◽  
In Vivo Experiments

AbstractCervical cancer, caused by human papillomavirus (HPV), is the fourth most common type of cancer among women worldwide. While HPV prophylactic vaccines are available, they have no therapeutic effects and do not clear up existing infections. This study aims to design a therapeutic vaccine against cervical cancer using reverse vaccinology. In this study, the E6 and E7 oncoproteins from HPV16 were chosen as the target antigens for epitope prediction. Cytotoxic T lymphocytes (CTL) and helper T lymphocytes (HTL) epitopes were predicted, and the best epitopes were selected based on antigenicity, allergenicity, and toxicity. The final vaccine construct was composed of the selected epitopes, along with the appropriate adjuvant and linkers. The multi-epitope vaccine was evaluated in terms of physicochemical properties, antigenicity, and allergenicity. The tertiary structure of the vaccine construct was predicted. Furthermore, several analyses were also carried out, including molecular docking, molecular dynamics (MD) simulation, and in silico cloning of the vaccine construct. The results showed that the final proposed vaccine could be considered an effective therapeutic vaccine for HPV; however, in vitro and in vivo experiments are required to validate the efficacy of this vaccine candidate.

The effects of photodynamic therapy with Photodithazine on HPV 16 E6/E7 associated cervical cancer model

2011 ◽  
Vol 15 (03) ◽  
pp. 174-180 ◽  
Author(s):  
Lan Ying Wen ◽  
Su-Mi Bae ◽  
Jin Hwan Do ◽  
Kye-Shin Park ◽  
Woong Shick Ahn
Keyword(s):  
Cervical Cancer ◽  
Photodynamic Therapy ◽  
Growth Inhibition ◽  
Biological Significance ◽  
Light Irradiation ◽  
Tumor Growth Inhibition ◽  
Cancer Model ◽  
Hpv 16

Photodynamic therapy (PDT) is a promising treatment for cancer that has been recently accepted in the clinic. In this study, we examined a biological significance of PDT with a chlorin-based photosensitizer, Photodithazine, on cervical cancer model. When human papillomavirus type 16 (HPV16)- transformed mouse TC-1 cells were exposed to varied doses of Photodithazine with light irradiation (6.25 J/cm2), the significant growth inhibition of TC-1 cells was observed at 0.75 μg/mL of Photodithazine. The damaged cells by Photodithazine/PDT were categorized to be early and late apoptosis, as determined by annexin V staining. Photodithazine was primarily localized at lysosome apparatus within TC-1 cells while it was rapidly accumulated and sustained for initial 3 h in tumor tissue of TC-1 tumor bearing mice after IV injection. The tumor growth inhibition by Photodithazine/PDT with light irradiation (300 J/cm2) was examined after injection of various concentration of Photodithazine in tumor mice system. Our results show that Photodithazine/PDT might have significant advantages in the selective killing of tumor lesions in HPV 16 E6/E7 associated cervical cancer model, both in vitro and in vivo.

Photodynamic effects of Radachlorin® on cervical cancer model

2005 ◽  
Vol 09 (12) ◽  
pp. 835-840 ◽  
Author(s):  
Sun-Young Kwak ◽  
Dae-Seog Lim ◽  
Su-Mi Bae ◽  
Yong-Wook Kim ◽  
Joon-Mo Lee ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Golgi Apparatus ◽  
Biological Significance ◽  
Annexin V ◽  
Light Irradiation ◽  
Control Group ◽  
Cancer Model ◽  
In Vivo Experiments

Photodynamic therapy (PDT) has been reported to be effective for treating various tumors and induce apoptosis in many tumor cells. In this study, we examined a biological significance of PDT with a chlorin-based photosensitizer, Radachlorin®, in a cervical cancer model, TC-1 cells. When TC-1 cells were exposed to varied doses of Radachlorin® with light irradiation (6.25 J/cm2), PDT induced a dose-dependent growth inhibition of TC-1 cells. All of these cells were significantly damaged after light irradiation and categorized to be early and late apoptosis, as determined by annexin V staining. Radachlorin® localized primarily into the Golgi apparatus of cells in 12 h of the treatment, and weak fluorescence intensity was also detected in mitochondria. On the other hand, in the in vivo experiments, following light irradiation (100 J/cm2), retarded tumor growth was significant in mice treated with Radachlorin®, as compared to the control group. Taken together, we propose that PDT after the application of Radachlorin® may induce the Golgi apparatus-mediated apoptosis of cervical cancer cells in vitro, and also be effective in the mice system.

scholarly journals Elevated Expression of lncRNA MEG3 Induces Endothelial Dysfunction on HUVECs of IVF Born Offspring via Epigenetic Regulation

2020 ◽  
Author(s):  
Ying Jiang ◽  
Hong Zhu ◽  
Hong Chen ◽  
Meng-Meng Yang ◽  
Yi-Chen Yu ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Umbilical Vein ◽  
Methylation Status ◽  
Vitro Fertilization ◽  
In Vivo Experiments ◽  
Elevated Expression ◽  
Nitrite Nitrate ◽  
Umbilical Vein Endothelial Cells

Abstract Background: The cardiovascular dysfunction in children born after in vitro fertilization (IVF) has been of great concern, in our study, we aim to explore potential molecular mechanism for such long-term outcomes. Methods：Real-time qPCR was used to test long non-coding RNA MEG3 and endothelium-derived factors, endothelial nitric oxide synthase (eNOS), endothelin-1(ET1), vascular endothelial growth factor (VEGF). Primary HUVEC after caesarean section was treated with different estradiol concentrations in vitro. Besides, knockdown of MEG3 on HUVEC provided further evidence between MEG3 expression and alteration of NO, ET1, VEGF. Then, by using pyrosequencing, we detected MEG3 promoter methylation status.Results: We found that the expression level of MEG3 was higher in human umbilical vein endothelial cells (HUVECs) of IVF offspring than that in spontaneously born offspring. Furthermore, we found decreased expression of eNOS, VEGF, elevated expression of ET1 in HUVECs from IVF offspring compared to spontaneously born offspring. We further confirmed the results from in-vivo experiments by demonstrating that high-estradiol intrauterine environments lead to abnormal expression of MEG3 and endothelium-derived factors. Meanwhile, silencing MEG3 expression decreased ET1 expression, and increased nitrite, nitrate, VEGF secretion, which could correct the effect we observed in-vivo. With pyrosequencing technology, we found that elevated expression of MEG3 in IVF offspring derived HUVECs was the result of hypomethylation of the MEG3 promoter. Conclusions: Our results demonstrated that higher expression of MEG3 in IVF-born HUVECs, accompanied by lower secretion of eNOS, VEGF, and higher secretion of ET1, which is closely related with endothelial dysfunction, which together provide a potential mechanism addressing high-risk of hypertension in IVF offspring.

scholarly journals Elevated expression of lncRNA MEG3 induces endothelial dysfunction on HUVECs of IVF born offspring via epigenetic regulation

2020 ◽  
Author(s):  
Ying Jiang ◽  
Hong Zhu ◽  
Hong Chen ◽  
Meng-Meng Yang ◽  
Yi-Chen Yu ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Umbilical Vein ◽  
Methylation Status ◽  
Vitro Fertilization ◽  
In Vivo Experiments ◽  
Elevated Expression ◽  
Nitrite Nitrate ◽  
Umbilical Vein Endothelial Cells

Abstract Background: The cardiovascular dysfunction in children born after in vitro fertilization (IVF) has been of great concern, in our study, we aim to explore potential molecular mechanism for such long-term outcomes. Methods： Real-time qPCR was used to test long non-coding RNAMEG3and endothelium-derived factors, endothelial nitric oxide synthase (eNOS), endothelin-1(ET1), vascular endothelial growth factor (VEGF). Primary HUVEC after caesarean section was treated with different estradiol concentrations in vitro. Besides, knockdown ofMEG3on HUVEC provided further evidence between MEG3 expression and alteration of NO, ET1, VEGF. Then, by using pyrosequencing, we detectedMEG3promoter methylation status. Results: We found that the expression level of MEG3was higher in human umbilical vein endothelial cells (HUVECs) of IVF offspring than that in spontaneously born offspring. Furthermore, we found decreased expression ofeNOS, VEGF, elevated expression of ET1in HUVECs from IVF offspring compared to spontaneously born offspring. We further confirmed the results from in-vivo experiments by demonstrating that high-estradiol intrauterine environments lead to abnormal expression of MEG3 and endothelium-derived factors. Meanwhile, silencing MEG3expression decreased ET1expression, and increased nitrite, nitrate, VEGFsecretion, which could correct the effect we observed in-vivo. With pyrosequencing technology, we found that elevated expression of MEG3in IVF offspring derived HUVECs was the result of hypomethylation of the MEG3promoter. Conclusions: Our results demonstrated that higher expression ofMEG3in IVF-born HUVECs, accompanied by lower secretion of eNOS, VEGF, and higher secretion of ET1, which is closely related with endothelial dysfunction, which togetherprovide a potential mechanism addressing high-risk of hypertension in IVF offspring.

scholarly journals Nuclear exosome HMGB3 secreted by nasopharyngeal carcinoma cells promotes tumour metastasis by inducing angiogenesis

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Kaiwen Zhang ◽  
Dong Liu ◽  
Jianmei Zhao ◽  
Si Shi ◽  
Xin He ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Umbilical Vein ◽  
High Mobility ◽  
Tumour Angiogenesis ◽  
In Vivo Experiments ◽  
Tumour Metastasis ◽  
Umbilical Vein Endothelial Cells ◽  
First Time

AbstractDistant metastasis accompanied by angiogenesis is the main cause of nasopharyngeal carcinoma (NPC)-related death. Nuclear exosomes (nEXOs) are potential tumour biomarkers. High mobility group box 3 (HMGB3), a nuclear protein, is known to be overexpressed in cancers. However, its role in NPC has not been elucidated. Here, we explore for the first time the function of nEXO HMGB3 in tumour angiogenesis involved in NPC metastasis using a series of in vitro experiments with NPC cell lines and clinical specimens and in vivo experiments with tumour xenograft zebrafish angiogenesis model. We found a high expression of HMGB3 in NPC, accompanied by the formation of micronuclei, to be associated with metastasis. Furthermore, the NPC-secreted HMGB3 expression was associated with tumour angiogenesis. Moreover, HMGB3-containing nEXOs, derived from the micronuclei of NPC cells, were ingested by the human umbilical vein endothelial cells (HUVECs), and accelerated angiogenesis in vitro and in vivo. Importantly, western blotting and flow cytometry analysis showed that circulating nEXO HMGB3 positively correlated with NPC metastasis. In summary, nEXO HMGB3 can be a significant biomarker of NPC metastasis and provide a novel basis for anti-angiogenesis therapy in clinical metastasis.

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