title: A role for microRNA-155 expression in microenvironment associated to HPV-induced carcinogenesis in K14-HPV16 transgenic mice.
abstract: Human Papillomavirus cause a number of diseases most notably cervical cancer. K14-HPV16 transgenic mice expressing the HPV16 early genes in squamous epithelial cells provide a suitable experimental model for studying these diseases. MicroRNAs are small non-coding RNAs that play an important role in regulating gene expression and have been suggested to play an important role in cancer development. The role of miR-155 in cancer remains controversial and there is limited evidence linking this miRNA to HPV- associated diseases. We hypothesized that miR-155 expression modulates each tissue's susceptibility to develop HPV-associated carcinogenesis. In this study, we analyzed miR-155 expression in ear and chest skin samples from 22-26 weeks old, female K14-HPV16 transgenic (HPV16+/-) and wild-type (HPV-/-) mice. Among wild-type mice the expression of miR-155 was lower in ear skin compared with chest skin (p = 0.028). In transgenic animals, in situ carcinoma was present in all ear samples whereas chest tissues only showed epidermal hyperplasia. Furthermore, in hyperplastic chest skin samples, miR-155 expression was lower than in normal chest skin (p = 0,026). These results suggest that miR-155 expression may modulate the microenvironmental susceptibility to cancer development and that high miR155 levels may be protective against the carcinogenesis induced by HPV16.
authors.affiliation: Molecular Oncology and Viral Pathology Group, CI-IPOP, Portuguese Institute of Oncology of Porto, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313, Porto, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Paiva
authors.affiliation: LEPABE, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias s/n, 4200-465, Porto, Portugal; Experimental Pathology and Therapeutics Group, CI-IPOP, Portuguese Institute of Oncology, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
authors.forename: Rui M
authors.initials: RM
authors.lastname: Gil da Costa
authors.affiliation: Molecular Oncology and Viral Pathology Group, CI-IPOP, Portuguese Institute of Oncology of Porto, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; Virology Service, Portuguese Institute of Oncology of Porto, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Ribeiro
authors.affiliation: Molecular Oncology and Viral Pathology Group, CI-IPOP, Portuguese Institute of Oncology of Porto, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; Virology Service, Portuguese Institute of Oncology of Porto, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
authors.forename: Hugo
authors.initials: H
authors.lastname: Sousa
authors.affiliation: LEPABE, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias s/n, 4200-465, Porto, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Bastos
authors.forename: Ana
authors.initials: A
authors.lastname: Faustino-Rocha
authors.affiliation: 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; Experimental Pathology and Therapeutics Group, CI-IPOP, Portuguese Institute of Oncology, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
authors.forename: Ana Faustino Carlos
authors.initials: AF
authors.lastname: Rocha
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
authors.affiliation: Veterinary Sciences Department, University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, 5001-801, Vila Real, Portugal; 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.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Oliveira
authors.affiliation: Molecular Oncology and Viral Pathology Group, CI-IPOP, Portuguese Institute of Oncology of Porto, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313, Porto, Portugal; Virology Service, Portuguese Institute of Oncology of Porto, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; CEBIMED, Faculty of Health Sciences of Fernando Pessoa University, Porto, Portugal; Portuguese League Against Cancer (Liga Portuguesa Contra o Cancro-Núcleo Regional do Norte), Estrada Interior da Circunvalação, n°6657, 4200-177 Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D002278:Carcinoma in Situ / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D004431:Ear, External / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D052162:Human papillomavirus 16 / Q000502:physiology*; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000502:physiology*; D030361:Papillomavirus Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse