Bacterial Species from Vaginal Microbiota Differently Affect the Production of the E6 and E7 Oncoproteins and of p53 and p-Rb Oncosuppressors in HPV16-Infected Cells
Vaginal dysbiosis is characterized by a decrease in the relative abundance of <i>Lactobacillus</i> species in favor of other species. This condition facilitates infections by sexually transmitted pathogens including high risk (HR)-human papilloma viruses (HPVs) involved in the developmen...
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MDPI AG
2023-04-01
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| author | Sabrina Nicolò Alberto Antonelli Michele Tanturli Ilaria Baccani Chiara Bonaiuto Giuseppe Castronovo Gian Maria Rossolini G. Mattiuz M. G. Torcia |
| author_facet | Sabrina Nicolò Alberto Antonelli Michele Tanturli Ilaria Baccani Chiara Bonaiuto Giuseppe Castronovo Gian Maria Rossolini G. Mattiuz M. G. Torcia |
| author_sort | Sabrina Nicolò |
| collection | DOAJ |
| description | Vaginal dysbiosis is characterized by a decrease in the relative abundance of <i>Lactobacillus</i> species in favor of other species. This condition facilitates infections by sexually transmitted pathogens including high risk (HR)-human papilloma viruses (HPVs) involved in the development of cervical cancer. Some vaginal dysbiosis bacteria contribute to the neoplastic progression by inducing chronic inflammation and directly activating molecular pathways involved in carcinogenesis. In this study, SiHa cells, an HPV-16-transformed epithelial cell line, were exposed to different representative vaginal microbial communities. The expression of the HPV oncogenes <i>E6</i> and <i>E7</i> and the production of relative oncoproteins was evaluated. The results showed that <i>Lactobacillus crispatus</i> and <i>Lactobacillus gasseri</i> modulated the basal expression of the <i>E6</i> and <i>E7</i> genes of SiHa cells and the production of the E6 and E7 oncoproteins. Vaginal dysbiosis bacteria had contrasting effects on <i>E6/E7</i> gene expression and protein production. The expression of the <i>E6</i> and <i>E7</i> genes and the production of the relative oncoproteins was increased by strains of <i>Gardnerella vaginalis</i> and, to a lesser extent, by <i>Megasphaera micronuciformis.</i> In contrast, <i>Prevotella bivia</i> decreased the expression of oncogenes and the production of the E7 protein. A decreased amount of p53 and pRb was found in the cultures of SiHa cells with <i>M. micronuciformis</i>, and accordingly, in the same cultures, a higher percentage of cells progressed to the S-phase of the cell cycle compared to the untreated or <i>Lactobacillus</i>-stimulated cultures. These data confirm that <i>L. crispatus</i> represents the most protective component of the vaginal microbiota against neoplastic progression of HR-HPV infected cells, while <i>M. micronuciformis</i> and, to a lesser extent, <i>G. vaginalis</i> may directly interfere in the oncogenic process, inducing or maintaining the production of viral oncoproteins. |
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| language | English |
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| spelling | doaj.art-5f3a75613f6d4be2a3ab7fe3c52108e52023-11-17T19:36:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248717310.3390/ijms24087173Bacterial Species from Vaginal Microbiota Differently Affect the Production of the E6 and E7 Oncoproteins and of p53 and p-Rb Oncosuppressors in HPV16-Infected CellsSabrina Nicolò0Alberto Antonelli1Michele Tanturli2Ilaria Baccani3Chiara Bonaiuto4Giuseppe Castronovo5Gian Maria Rossolini6G. Mattiuz7M. G. Torcia8Department of Clinical and Experimental Medicine, University of Florence, 50134 Florence, ItalyDepartment of Clinical and Experimental Medicine, University of Florence, 50134 Florence, ItalyDepartment of Clinical and Experimental Medicine, University of Florence, 50134 Florence, ItalyDepartment of Clinical and Experimental Medicine, University of Florence, 50134 Florence, ItalyDepartment of Clinical and Experimental Medicine, University of Florence, 50134 Florence, ItalyDepartment of Clinical and Experimental Medicine, University of Florence, 50134 Florence, ItalyDepartment of Clinical and Experimental Medicine, University of Florence, 50134 Florence, ItalyDepartment of Clinical and Experimental Medicine, University of Florence, 50134 Florence, ItalyDepartment of Clinical and Experimental Medicine, University of Florence, 50134 Florence, ItalyVaginal dysbiosis is characterized by a decrease in the relative abundance of <i>Lactobacillus</i> species in favor of other species. This condition facilitates infections by sexually transmitted pathogens including high risk (HR)-human papilloma viruses (HPVs) involved in the development of cervical cancer. Some vaginal dysbiosis bacteria contribute to the neoplastic progression by inducing chronic inflammation and directly activating molecular pathways involved in carcinogenesis. In this study, SiHa cells, an HPV-16-transformed epithelial cell line, were exposed to different representative vaginal microbial communities. The expression of the HPV oncogenes <i>E6</i> and <i>E7</i> and the production of relative oncoproteins was evaluated. The results showed that <i>Lactobacillus crispatus</i> and <i>Lactobacillus gasseri</i> modulated the basal expression of the <i>E6</i> and <i>E7</i> genes of SiHa cells and the production of the E6 and E7 oncoproteins. Vaginal dysbiosis bacteria had contrasting effects on <i>E6/E7</i> gene expression and protein production. The expression of the <i>E6</i> and <i>E7</i> genes and the production of the relative oncoproteins was increased by strains of <i>Gardnerella vaginalis</i> and, to a lesser extent, by <i>Megasphaera micronuciformis.</i> In contrast, <i>Prevotella bivia</i> decreased the expression of oncogenes and the production of the E7 protein. A decreased amount of p53 and pRb was found in the cultures of SiHa cells with <i>M. micronuciformis</i>, and accordingly, in the same cultures, a higher percentage of cells progressed to the S-phase of the cell cycle compared to the untreated or <i>Lactobacillus</i>-stimulated cultures. These data confirm that <i>L. crispatus</i> represents the most protective component of the vaginal microbiota against neoplastic progression of HR-HPV infected cells, while <i>M. micronuciformis</i> and, to a lesser extent, <i>G. vaginalis</i> may directly interfere in the oncogenic process, inducing or maintaining the production of viral oncoproteins.https://www.mdpi.com/1422-0067/24/8/7173HR-HPV (high-risk human papillomavirus)CIN-1 (low grade of cervical intraepithelial neoplasia)<i>Lactobacillus</i><i>Gardnerella</i><i>Megasphaera</i>E6 and E7 oncoproteins |
| spellingShingle | Sabrina Nicolò Alberto Antonelli Michele Tanturli Ilaria Baccani Chiara Bonaiuto Giuseppe Castronovo Gian Maria Rossolini G. Mattiuz M. G. Torcia Bacterial Species from Vaginal Microbiota Differently Affect the Production of the E6 and E7 Oncoproteins and of p53 and p-Rb Oncosuppressors in HPV16-Infected Cells International Journal of Molecular Sciences HR-HPV (high-risk human papillomavirus) CIN-1 (low grade of cervical intraepithelial neoplasia) <i>Lactobacillus</i> <i>Gardnerella</i> <i>Megasphaera</i> E6 and E7 oncoproteins |
| title | Bacterial Species from Vaginal Microbiota Differently Affect the Production of the E6 and E7 Oncoproteins and of p53 and p-Rb Oncosuppressors in HPV16-Infected Cells |
| title_full | Bacterial Species from Vaginal Microbiota Differently Affect the Production of the E6 and E7 Oncoproteins and of p53 and p-Rb Oncosuppressors in HPV16-Infected Cells |
| title_fullStr | Bacterial Species from Vaginal Microbiota Differently Affect the Production of the E6 and E7 Oncoproteins and of p53 and p-Rb Oncosuppressors in HPV16-Infected Cells |
| title_full_unstemmed | Bacterial Species from Vaginal Microbiota Differently Affect the Production of the E6 and E7 Oncoproteins and of p53 and p-Rb Oncosuppressors in HPV16-Infected Cells |
| title_short | Bacterial Species from Vaginal Microbiota Differently Affect the Production of the E6 and E7 Oncoproteins and of p53 and p-Rb Oncosuppressors in HPV16-Infected Cells |
| title_sort | bacterial species from vaginal microbiota differently affect the production of the e6 and e7 oncoproteins and of p53 and p rb oncosuppressors in hpv16 infected cells |
| topic | HR-HPV (high-risk human papillomavirus) CIN-1 (low grade of cervical intraepithelial neoplasia) <i>Lactobacillus</i> <i>Gardnerella</i> <i>Megasphaera</i> E6 and E7 oncoproteins |
| url | https://www.mdpi.com/1422-0067/24/8/7173 |
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