1. Dysregulated expression of microRNA-150 in human papillomavirus-induced lesions of K14-HPV16 transgenic mice.
- Author
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Santos, Joana M.O., Fernandes, Mara, Araújo, Rita, Sousa, Hugo, Ribeiro, Joana, Bastos, Margarida M.S.M., Oliveira, Paula A., Carmo, Diogo, Casaca, Fátima, Silva, Sandra, Teixeira, Ana L., Gil da Costa, Rui M., and Medeiros, Rui
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MICRORNA , *CARCINOGENICITY , *CARCINOGENICITY testing , *NON-coding RNA , *PAPILLOMAVIRUSES , *SQUAMOUS cell carcinoma - Abstract
Aims 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. Main 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. Key findings 24–26 weeks-old HPV +/− mice showed diffuse epidermal hyperplasia and focal dysplasia in a hyperplastic background (31.8% incidence), but 28–30 weeks-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). Significance 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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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