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Author(s): Isabel Paiva
Rui M. Gil da Costa
Joana Ribeiro
Hugo Sousa
Margarida M. S. M. Bastos
Ana Faustino Rocha
Carlos Lopes
Paula A. Oliveira
Rui Medeiros
Title: MicroRNA-21 expression and susceptibility to HPV-induced carcinogenesis - role of microenvironment in K14-HPV16 mice model
Issue Date: 2015
Abstract: Aims: Human papillomaviruses (HPVs) are responsible for several types of cancer. K14-HPV16 transgenic mice express the HPV16 early genes, developing multi-step carcinogenesis associated with marked inflammation, as observed in human patients. MicroRNAs (MiRNA) constitute a class of non-coding RNAs that regulate gene expression. In particular, miR-21 has been associated with carcinogenesis. However, little is known about this microRNA in the normal tissue microenvironment and its possible relationship with cancer predisposition. We hypothesized that miR-21 expression influences each tissue's susceptibility to HPV-induced carcinogenesis. Main methods: In order to test this hypothesis, we evaluated miR-21 expression by RT-qPCR in ear and chest skin samples from 24-28 weeks old, female K14-HPV16 transgenic and wild-type mice. Key findings: In wild-type mice (HPV-/-) miR-21 expression was lower in ear skin compared with that of chest skin (p = 0.036). Under the influence of HPV16 oncogenes, transgenic animals (HPV16+/-), developed in situ carcinoma in all ear samples and epidermal hyperplasia in chest samples. These results are consistent with the hypothesis that microRNA expression in the microenvironment of normal tissues may influence HPV-associated carcinogenesis. Furthermore, among transgenic animals, miR-21 expression was lower in in situ carcinoma samples compared with hyperplasia (p = 0043). Significance: This suggests that, despite the well-known role of miR-21 as an oncogene, its anti-inflammatory and immunomodulatory properties may modulate HPV-induced carcinogenesis in a tissue-dependent manner. Further studies are warranted in order to explore the role of microRNAs in tissue susceptibility to carcinogenesis.
Related Information: info:eu-repo/grantAgreement/FCT - Fundação para a Ciência e Tecnologia/Projetos Estratégicos/UID/EQU/00511/2013 - POCI-01-0145-FEDER-006939/Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia/LEPABE
Document Type: Artigo em Revista Científica Internacional
Rights: restrictedAccess
Appears in Collections:FEUP - Artigo em Revista Científica Internacional
ICBAS - Artigo em Revista Científica Internacional

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