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Journal of Cancer Research and Clinical Oncology

Published in:

01-02-2018 | Original Article – Cancer Research

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

Authors: Rita Araújo, Joana M. O. Santos, Mara Fernandes, Francisca Dias, Hugo Sousa, Joana Ribeiro, Margarida M. S. M. Bastos, Paula A. Oliveira, Diogo Carmo, Fátima Casaca, Sandra Silva, Rui Medeiros, Rui M. Gil da Costa

Published in: Journal of Cancer Research and Clinical Oncology | Issue 2/2018

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.

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Title: Expression profile of microRNA-146a along HPV-induced multistep carcinogenesis: a study in HPV16 transgenic mice
Authors: Rita Araújo
Joana M. O. Santos
Mara Fernandes
Francisca Dias
Hugo Sousa
Joana Ribeiro
Margarida M. S. M. Bastos
Paula A. Oliveira
Diogo Carmo
Fátima Casaca
Sandra Silva
Rui Medeiros
Rui M. Gil da Costa
Publication date: 01-02-2018
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 2/2018
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-017-2549-5

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

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

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Conclusions

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