Rita Araújo1,2, Joana M O Santos1,3,4, Mara Fernandes1,3,4, Francisca Dias1,2, Hugo Sousa1,5, Joana Ribeiro1,3,5, Margarida M S M Bastos6, Paula A Oliveira7,8, Diogo Carmo9, Fátima Casaca9, Sandra Silva9, Rui Medeiros10,11,12,13,14, Rui M Gil da Costa1,6,7. 1. Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal. 2. Abel Salazar Institute of Biomedical Sciences of the University of Porto (ICBAS), Rua de Jorge Viterbo Ferreira 228, 4050-313, Porto, Portugal. 3. Faculty of Medicine of the University of Porto (FMUP), Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal. 4. Research Department, Portuguese League Against Cancer (Liga Portuguesa Contra o Cancro - Núcleo Regional do Norte), Estrada Interior da Circunvalação, no. 6657, 4200-177, Porto, Portugal. 5. Virology Service, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal. 6. Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE), Faculty of Engineering of the University of Porto (FEUP), Rua Dr. Roberto Frias s/n, 4200-465, Porto, Portugal. 7. Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5001-911, Vila Real, Portugal. 8. Veterinary Sciences Department, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5001-801, Vila Real, Portugal. 9. Botelho Moniz Análises Clínicas (BMAC), Rua Sarmento de Beires 153, 4250-449, Porto, Portugal. 10. Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal. ruimedei@ipoporto.min-saude.pt. 11. Faculty of Medicine of the University of Porto (FMUP), Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal. ruimedei@ipoporto.min-saude.pt. 12. Research Department, Portuguese League Against Cancer (Liga Portuguesa Contra o Cancro - Núcleo Regional do Norte), Estrada Interior da Circunvalação, no. 6657, 4200-177, Porto, Portugal. ruimedei@ipoporto.min-saude.pt. 13. Virology Service, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal. ruimedei@ipoporto.min-saude.pt. 14. Biomedical Research Centre (CEBIMED), Faculty of Health Sciences of the Fernando Pessoa University, Porto, Portugal. ruimedei@ipoporto.min-saude.pt.
Abstract
PURPOSE: Persistent human papillomavirus (HPV) infection is associated with the development of certain types of cancer and the dysregulation of microRNAs has been implicated in HPV-associated carcinogenesis. This is the case of microRNA-146a (miR-146a), which is thought to regulate tumor-associated inflammation. We sought to investigate the expression levels of miR-146a during HPV16-mediated carcinogenesis using skin samples from K14-HPV16 transgenic mice which develop the consecutive phases of the carcinogenesis process. METHODS: Female transgenic (HPV+/-) and wild-type (HPV-/-) mice were sacrificed at 24-26 weeks-old or 28-30 weeks-old. Chest and ear skin samples from HPV+/- and HPV-/- mice were histologically classified and used for microRNA extraction and quantification by qPCR. RESULTS: Chest skin samples from 24 to 26 weeks-old HPV+/- mice presented diffuse epidermal hyperplasia and only 22.5% showed multifocal dysplasia, while at 28-30 weeks-old all (100.0%) HPV+/- animals showed epidermal dysplasia. All HPV+/- ear skin samples showed carcinoma in situ (CIS). MiR-146a expression levels were higher in HPV+/- compared to HPV-/- mice (p = 0.006). There was also an increase in miR-146a expression in dysplastic skin lesions compared with hyperplasic lesions (p = 0.011). Samples showing CIS had a significant decrease in miR-146a expression when compared to samples showing epidermal hyperplasia (p = 0.018) and epidermal dysplasia (p = 0.009). CONCLUSIONS: These results suggest that HPV16 induces the overexpression of miR-146a in the initial stages of carcinogenesis (hyperplasia and dysplasia), whereas decreases its expression at later stages (CIS). Taken together, these data implicate and suggest different roles of miR-146a in HPV-mediated carcinogenesis.
PURPOSE: Persistent human papillomavirus (HPV) infection is associated with the development of certain types of cancer and the dysregulation of microRNAs has been implicated in HPV-associated carcinogenesis. This is the case of microRNA-146a (miR-146a), which is thought to regulate tumor-associated inflammation. We sought to investigate the expression levels of miR-146a during HPV16-mediated carcinogenesis using skin samples from K14-HPV16transgenic mice which develop the consecutive phases of the carcinogenesis process. METHODS: Female transgenic (HPV+/-) and wild-type (HPV-/-) mice were sacrificed at 24-26 weeks-old or 28-30 weeks-old. Chest and ear skin samples from HPV+/- and HPV-/- mice were histologically classified and used for microRNA extraction and quantification by qPCR. RESULTS: Chest skin samples from 24 to 26 weeks-old HPV+/- mice presented diffuse epidermal hyperplasia and only 22.5% showed multifocal dysplasia, while at 28-30 weeks-old all (100.0%) HPV+/- animals showed epidermal dysplasia. All HPV+/- ear skin samples showed carcinoma in situ (CIS). MiR-146a expression levels were higher in HPV+/- compared to HPV-/- mice (p = 0.006). There was also an increase in miR-146a expression in dysplastic skin lesions compared with hyperplasic lesions (p = 0.011). Samples showing CIS had a significant decrease in miR-146a expression when compared to samples showing epidermal hyperplasia (p = 0.018) and epidermal dysplasia (p = 0.009). CONCLUSIONS: These results suggest that HPV16 induces the overexpression of miR-146a in the initial stages of carcinogenesis (hyperplasia and dysplasia), whereas decreases its expression at later stages (CIS). Taken together, these data implicate and suggest different roles of miR-146a in HPV-mediated carcinogenesis.
Authors: Carlos Santos; Pedro Ferreirinha; Hugo Sousa; Joana Ribeiro; Margarida M S M Bastos; Tiago Neto; Paula A Oliveira; Rui Medeiros; Manuel Vilanova; Rui M Gil da Costa Journal: Food Chem Toxicol Date: 2016-09-15 Impact factor: 6.023
Authors: Alexandra C Costa; Joana M O Santos; Beatriz Medeiros-Fonseca; Paula A Oliveira; Margarida M S M Bastos; Haissa O Brito; Rui M Gil da Costa; Rui Medeiros Journal: Cancers (Basel) Date: 2022-04-28 Impact factor: 6.575
Authors: Joana M O Santos; Sara Peixoto da Silva; Natália R Costa; Rui M Gil da Costa; Rui Medeiros Journal: Cancers (Basel) Date: 2018-12-05 Impact factor: 6.639