Dysregulated expression of microRNA-150 in human papillomavirus-induced lesions of K14-HPV16 transgenic mice

被引:11
|
作者
Santos, Joana M. O. [1 ,2 ]
Fernandes, Mara [1 ,3 ,4 ]
Araujo, Rita [1 ,2 ]
Sousa, Hugo [1 ,5 ]
Ribeiro, Joana [1 ,5 ]
Bastos, Margarida M. S. M. [6 ]
Oliveira, Paula A. [7 ,8 ]
Carmo, Diogo [9 ]
Casaca, Fatima [9 ]
Silva, Sandra [9 ]
Teixeira, Ana L. [1 ,4 ]
da Costa, Rui M. Gil [1 ,6 ,7 ]
Medeiros, Rui [1 ,2 ,4 ,5 ,10 ]
机构
[1] Portuguese Inst Oncol Porto IPO Porto, IPO Porto Res Ctr CI IPOP, Mol Oncol & Viral Pathol Grp, Rua Dr Antonio Bernardino de Almeida, P-4200072 Oporto, Portugal
[2] Univ Porto, Abel Salazar Inst Biomed Sci, ICBAS, Rua Jorge Viterbo Ferreira 228, P-4050313 Oporto, Portugal
[3] Univ Porto, Fac Med, FMUP, Alameda Prof Hernani Monteiro, P-4200319 Oporto, Portugal
[4] Portuguese League Canc, Res Dept, LPCC, Nucleo Reg Norte, Estr Interior Circunvalacao 6657, P-4200177 Oporto, Portugal
[5] Portuguese Inst Oncol Porto, Virol Serv, Rua Dr Antonio Bernardino de Almeida, P-4200072 Oporto, Portugal
[6] Univ Porto, Fac Engn, LEPABE, Rua Dr Roberto Fries S-N, P-4200465 Oporto, Portugal
[7] Univ Tras Os Montes & Alto Douro, Ctr Res & Technol Agroenvironm & Biol Sci CITAB, UTAD, P-5001911 Quinta De Prados, Vila Real, Portugal
[8] Univ Tras Os Montes & Alto Douro, Vet Sci Dept, UTAD, P-5001801 Quinta De Prados, Vila Real, Portugal
[9] BMAC, Rua Sarmento de Beires 153, P-4250449 Oporto, Portugal
[10] Fernando Pessoa Univ, Fac Hlth Sci, CEBIMED, Oporto, Portugal
关键词
HPV16; miRNA-150; K14-HPV16 transgenic mice; Hyperplasia; Dysplasia; CD8(+) T-CELLS; CANCER; MIR-150; CARCINOMA; E6; CARCINOGENESIS; PROGNOSIS; HEAD;
D O I
10.1016/j.lfs.2017.03.008
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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). MiR150 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. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:31 / 36
页数:6
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