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
相关论文
共 50 条
  • [41] Co-Expression of p53 and Bcl-2 Proteins in Human Papillomavirus-Induced Premalignant Lesions of the Uterine Cervix: Correlation with Progression to Malignancy
    Singh, Madhulika
    Srivastava, Smita
    Singh, Uma
    Mathur, Neeraj
    Shukla, Yogeshwer
    TUMOR BIOLOGY, 2009, 30 (5-6) : 276 - 285
  • [42] TISSUE-SPECIFIC AND DIFFERENTIATION-SPECIFIC EXPRESSION OF A HUMAN K14 KERATIN GENE IN TRANSGENIC MICE
    VASSAR, R
    ROSENBERG, M
    ROSS, S
    TYNER, A
    FUCHS, E
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (05) : 1563 - 1567
  • [43] ABROGATED NK-CELL LYSIS OF HUMAN PAPILLOMAVIRUS (HPV)-16-BEARING KERATINOCYTES IN PATIENTS WITH PRE-CANCEROUS AND CANCEROUS HPV-INDUCED ANOGENITAL LESIONS
    MALEJCZYK, J
    MAJEWSKI, S
    JABLONSKA, S
    ROGOZINSKI, TT
    ORTH, G
    INTERNATIONAL JOURNAL OF CANCER, 1989, 43 (02) : 209 - 214
  • [44] Development of spontaneous hyperplastic skin lesions and chemically induced skin papillomas in transgenic mice expressing human papillomavirus type 16 E6/E7 genes
    Kang, JK
    Kim, JH
    Lee, SH
    Kim, DH
    Kim, HS
    Lee, JE
    Seo, JS
    CANCER LETTERS, 2000, 160 (02) : 177 - 183
  • [45] EPIDERMOTROPISM OF T-CELLS CORRELATES WITH INTERCELLULAR-ADHESION MOLECULE (ICAM1) EXPRESSION IN HUMAN PAPILLOMAVIRUS (HPV)-INDUCED LESIONS
    VIAC, J
    CHARDONNET, Y
    EUVRARD, S
    SCHMITT, D
    JOURNAL OF PATHOLOGY, 1992, 168 (03): : 301 - 306
  • [46] Expression of p16 in Low-Grade Squamous Intraepithelial Lesions (LSIL/CIN 1): Correlation of Immunohistochemical Staining Patterns with Analysis of Human Papillomavirus (HPV) Types
    Yemelyanova, A.
    Ronnett, B. M.
    Seidman, J. D.
    Ogurtsova, A.
    Gravitt, P. E.
    MODERN PATHOLOGY, 2013, 26 : 299A - 299A
  • [47] Expression of p16 in Low-Grade Squamous Intraepithelial Lesions (LSIL/CIN 1): Correlation of Immunohistochemical Staining Patterns with Analysis of Human Papillomavirus (HPV) Types
    Yemelyanova, A.
    Ronnett, B. M.
    Seidman, J. D.
    Ogurtsova, A.
    Gravitt, P. E.
    LABORATORY INVESTIGATION, 2013, 93 : 299A - 299A
  • [48] EXPRESSION AND SPLICING PATTERNS OF HUMAN PAPILLOMAVIRUS TYPE-16 MESSENGER-RNAS IN PRECANCEROUS LESIONS AND CARCINOMAS OF THE CERVIX, IN HUMAN KERATINOCYTES IMMORTALIZED BY HPV-16, AND IN CELL-LINES ESTABLISHED FROM CERVICAL CANCERS
    SHERMAN, L
    ALLOUL, N
    GOLAN, I
    DURST, M
    BARAM, A
    INTERNATIONAL JOURNAL OF CANCER, 1992, 50 (03) : 356 - 364
  • [49] The study of immunogenicity of the antigenic protein of high risk oncogenic type of the human papillomavirus HPV16 L1 produced in the plant expression system on the base of transgenic tomato
    R. K. Salyaev
    N. I. Rekoslavskaya
    A. S. Stolbikov
    A. V. Tretyakova
    Doklady Biochemistry and Biophysics, 2017, 474 : 186 - 188
  • [50] The study of immunogenicity of the antigenic protein of high risk oncogenic type of the human papillomavirus HPV16 L1 produced in the plant expression system on the base of transgenic tomato
    Salyaev, R. K.
    Rekoslavskaya, N. I.
    Stolbikov, A. S.
    Tretyakova, A. V.
    DOKLADY BIOCHEMISTRY AND BIOPHYSICS, 2017, 474 (01) : 186 - 188