The role of microRNAs 371 and 34a in androgen receptor control influencing prostate cancer behavior
Carregando...
Citações na Scopus
10
Tipo de produção
article
Data de publicação
2015
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER SCIENCE INC
Citação
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS, v.33, n.6, 2015
Resumo
Background: The molecular mechanisms involved in androgen receptor (AR) signaling pathways are not completely understood, and deregulation of microRNAs (miRNAs) expression may play a role in prostate cancer (PC) development and progression. Methods: The expression levels of miRNA and AR were evaluated with quantitative real-time polymerase chain reaction using frozen tissue from the surgical specimens of 83 patients submitted to radical prostatectomy. The expression level of miRNAs was correlated with prognostic factors and biochemical recurrence during a follow-up period of 45 months. In vitro and in vivo experiments were performed to understand the effect of miRNAs over AR in the context of that seen in a PC model. Results: MiR-371 underexpression correlated with non-organ-confined (pT3) disease (P = 0.009). In vitro transfection of miR-371 reduced the levels of AR by 22% and 28% in LNCaP and PC3 cell lines, respectively, and in kallikrein 3, it was reduced by 51%. PC was induced in Balb/c mice using PC-3M-luc-C6 cells, and animals were treated with 3 local doses of miR-371. Tumor growth evaluated by in vivo imaging after luciferase injection was slower in animals treated with miR-371. To explore further the possible role of miRNAs in the AR pathway, LNCaP cell line was treated with 5 alpha-dihydrotestosterone and flutamide showing alteration in miRNAs expression, especially miR-34a, which was significantly underexpressed after treatment with high doses of 5 alpha-dihydrotestosterone. Conclusion: Our data support a role for miRNAs, especially miR-371 and miR-34a, in the complex disarrangement of AR signaling pathway and in the behavior of PC.
Palavras-chave
Prostate cancer, MicroRNAs, Androgen receptor, Prognosis, In vitro, In vivo, Cell lines
Referências
- Agostini M, 2014, ONCOTARGET, V5, P872
- Brabletz T, 2012, CELL CYCLE, V11, P215, DOI 10.4161/cc.11.2.18900
- Cairo S, 2010, P NATL ACAD SCI USA, V107, P20471, DOI 10.1073/pnas.1009009107
- Chen CD, 2004, NAT MED, V10, P33, DOI 10.1038/nm972
- Ghawanmeh T, 2011, ONCOLOGY-BASEL, V81, P330, DOI 10.1159/000334237
- Hamada A, 2008, CLIN CANCER RES, V14, P3312, DOI 10.1158/1078-0432.CCR-07-4118
- Henrich KO, 2012, CANCER RES, V72, P6079, DOI 10.1158/0008-5472.CAN-12-2230
- Kracikova M, 2013, CELL DEATH DIFFER, V20, P576, DOI 10.1038/cdd.2012.155
- Liu C, 2011, NAT MED, V17, P211, DOI 10.1038/nm.2284
- Liu RY, 2013, CANCER LETT, V335, P351, DOI 10.1016/j.canlet.2013.02.045
- Mohler JL, 2004, CLIN CANCER RES, V10, P440, DOI 10.1158/1078-0432.CCR-1146-03
- Murray MJ, 2011, AM J CLIN PATHOL, V135, P119, DOI 10.1309/AJCPOE11KEYZCJHT
- Ostling P, 2011, CANCER RES, V71, P1956, DOI 10.1158/0008-5472.CAN-10-2421
- Ryan CJ, 2011, J CLIN ONCOL, V29, P3651, DOI 10.1200/JCO.2011.35.2005
- Sun F, 2008, FEBS LETT, V582, P1564, DOI 10.1016/j.febslet.2008.03.057
- Sun SH, 2010, J CLIN INVEST, V120, P2715, DOI 10.1172/JCI41824
- Takeshita F, 2010, MOL THER, V18, P181, DOI 10.1038/mt.2009.207
- TAPLIN ME, 1995, NEW ENGL J MED, V332, P1393, DOI 10.1056/NEJM199505253322101
- Wang WLW, 2011, MOL CANCER, V10, DOI 10.1186/1476-4598-10-58
- Yousef GM, 2008, BIOL CHEM, V389, P689, DOI 10.1515/BC.2008.068
- Yousef GM, 2001, ENDOCR REV, V22, P184, DOI 10.1210/er.22.2.184