Expression profile of microRNA-146a along HPV-induced multistep carcinogenesis: a study in HPV16 transgenic mice

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Rita Araújo (Author) Other; Joana M. O. Santos (Author) Other; Mara Fernandes (Author) Other; Francisca Dias (Author) Other; Hugo Sousa (Author) Other; Joana Ribeiro (Author) Other; Margarida M. S. M. Bastos (Author) FEUP; Paula A. Oliveira (Author) Other; Diogo Carmo (Author) Other; Fátima Casaca (Author) Other; Sandra Silva (Author) Other; Rui Medeiros (Author) Other; Rui M. Gil da Costa (Author) FEUP

Journal

Title: Journal of Cancer Research and Clinical Oncology

Vol. 144

Pages: 241-248

ISSN: 0171-5216

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 11 Citations

Scopus - 14 Citations

Associated Projects

LEPABE - Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia

Other information

Authenticus ID: P-00N-8V7

DOI: 10.1007/s00432-017-2549-5

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8