title: Dysregulated expression of microRNA-150 in human papillomavirus-induced lesions of K14-HPV16 transgenic mice.
abstract: OBJECTIVE
  High-risk human papillomavirus (HPV) infection is one of the major causes of infection-related cancers worldwide. MicroRNAs (miRNAs) are a family of non-coding RNAs (ncRNAs), whose dysregulated levels may cause an aberrant expression of genes involved in oncogenic pathways and consequently lead to cancer development. This is the case of the miRNA-150 (miR-150), whose expression in HPV-induced lesions remains unclear and the present work aims to clarify it. We employed K14-HPV16 mice, which express the early genes of HPV16 in basal keratinocytes, leading to the development of hyperplastic and dysplastic skin lesions and squamous cell carcinomas, and are a representative model of HPV-induced cancers.
  
  
  METHODS
  In order to evaluate the expression of miR-150 in HPV-induced lesions, we performed qPCR in wild-type mice (HPV-/-) and in skin lesions of K14-HPV16 transgenic mice (HPV+/-). Matched skin samples were analyzed histologically.
  
  
  RESULTS
  24-26weeks-old HPV+/-mice showed diffuse epidermal hyperplasia and focal dysplasia in a hyperplastic background (31.8% incidence), but 28-30weeks-old HPV+/-mice presented higher incidence of dysplasia (100.0%). MiR-150 was upregulated in HPV+/-mice when compared with HPV-/-mice (p<0.001). MiR-150 was also overexpressed in diffuse dysplastic lesions when compared with hyperplastic lesions (p=0.005).
  
  
  CONCLUSIONS
  The present results suggest that miR-150 is overexpressed in HPV-induced lesions in this model and its expression seems to increase with lesion progression, along the process of multi-step carcinogenesis.
authors.affiliation: Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO-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: Joana M O
authors.initials: JMO
authors.lastname: Santos
authors.affiliation: Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; FMUP, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal; LPCC, 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.
authors.forename: Mara
authors.initials: M
authors.lastname: Fernandes
authors.affiliation: Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO-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: Rita
authors.initials: R
authors.lastname: Araújo
authors.affiliation: Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO-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: Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO-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: LEPABE, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal.
authors.forename: Margarida M S M
authors.initials: MMSM
authors.lastname: Bastos
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; Veterinary Sciences Department, University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, 5001-801 Vila Real, Portugal.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Oliveira
authors.affiliation: Botelho Moniz Análises Clínicas (BMAC), Rua Sarmento de Beires 153, 4250-449 Porto, Portugal.
authors.forename: Diogo
authors.initials: D
authors.lastname: Carmo
authors.affiliation: Botelho Moniz Análises Clínicas (BMAC), Rua Sarmento de Beires 153, 4250-449 Porto, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Casaca
authors.affiliation: Botelho Moniz Análises Clínicas (BMAC), Rua Sarmento de Beires 153, 4250-449 Porto, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Silva
authors.affiliation: Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; LPCC, 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.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Teixeira
authors.affiliation: Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; LEPABE, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, 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: Rui M
authors.initials: RM
authors.lastname: Gil da Costa
authors.affiliation: Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO-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; LPCC, 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; Virology Service, Portuguese Institute of Oncology of Porto, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; CEBIMED, Faculty of Health Sciences, Fernando Pessoa University, Porto, Portugal. Electronic address: ruimedei@ipoporto.min-saude.pt.
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C529101:Mirn150 microRNA, mouse
keywords: Dysplasia; HPV16; Hyperplasia; K14-HPV16 transgenic mice; miRNA-150