PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling

BMC Cancer

Research Article

Etel Rodrigues Pereira Gimba¹  Cinthya Sternberg²  Luciana Bueno Ferreira²  Mauricio S Caetano²  Kivvi Duarte de Mello²  Luiz Ricardo Goulart³  Adriana Freitas Neves⁴  Felipe Leite de Oliveira⁵  Luiz Eurico Nasciutti⁵  Antonio Palumbo⁵ 

[1] Instituto Nacional do Câncer/Programa de Carcinogênese Molecular and Programa de Pós Graduação Stricto Sensu em Oncologia, Rio de Janeiro, Brazil;Department of Medical Microbiology and Immunology, University of California-Davis, Davis, CA, USA;Universidade Federal Fluminense, Rio de Janeiro, Rio de Janeiro, Brazil;Departamento Interdisciplinar, Universidade Federal Fluminense-PURO, Rua Recife s/n, CEP: 28890-000, Rio das Ostras, Rio de Janeiro, Brazil;Instituto Nacional do Câncer/Programa de Carcinogênese Molecular and Programa de Pós Graduação Stricto Sensu em Oncologia, Rio de Janeiro, Brazil;Universidade Federal Fluminense, Rio de Janeiro, Rio de Janeiro, Brazil;Universidade Federal de Goiás, Campus de Catalão, Goiás, Brazil;Instituto de Genética e Bioquímica, Laboratório de Nanobiotecnologia, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil;Universidade Federal Fluminense, Rio de Janeiro, Rio de Janeiro, Brazil;Universidade Federal de Goiás, Campus de Catalão, Goiás, Brazil;Universidade Federal Fluminense, Rio de Janeiro, Rio de Janeiro, Brazil;Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Universidade Federal Fluminense, Rio de Janeiro, Rio de Janeiro, Brazil;

关键词: PCA3;    Prostate cancer;    Small interfering RNA;    Cell survival;    Noncoding RNA;   

DOI  :  10.1186/1471-2407-12-507

 received in 2012-05-15, accepted in 2012-10-19,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundPCA3 is a non-coding RNA (ncRNA) that is highly expressed in prostate cancer (PCa) cells, but its functional role is unknown. To investigate its putative function in PCa biology, we used gene expression knockdown by small interference RNA, and also analyzed its involvement in androgen receptor (AR) signaling.MethodsLNCaP and PC3 cells were used as in vitro models for these functional assays, and three different siRNA sequences were specifically designed to target PCA3 exon 4. Transfected cells were analyzed by real-time qRT-PCR and cell growth, viability, and apoptosis assays. Associations between PCA3 and the androgen-receptor (AR) signaling pathway were investigated by treating LNCaP cells with 100 nM dihydrotestosterone (DHT) and with its antagonist (flutamide), and analyzing the expression of some AR-modulated genes (TMPRSS2, NDRG1, GREB1, PSA, AR, FGF8, CdK1, CdK2 and PMEPA1). PCA3 expression levels were investigated in different cell compartments by using differential centrifugation and qRT-PCR.ResultsLNCaP siPCA3-transfected cells significantly inhibited cell growth and viability, and increased the proportion of cells in the sub G0/G1 phase of the cell cycle and the percentage of pyknotic nuclei, compared to those transfected with scramble siRNA (siSCr)-transfected cells. DHT-treated LNCaP cells induced a significant upregulation of PCA3 expression, which was reversed by flutamide. In siPCA3/LNCaP-transfected cells, the expression of AR target genes was downregulated compared to siSCr-transfected cells. The siPCA3 transfection also counteracted DHT stimulatory effects on the AR signaling cascade, significantly downregulating expression of the AR target gene. Analysis of PCA3 expression in different cell compartments provided evidence that the main functional roles of PCA3 occur in the nuclei and microsomal cell fractions.ConclusionsOur findings suggest that the ncRNA PCA3 is involved in the control of PCa cell survival, in part through modulating AR signaling, which may raise new possibilities of using PCA3 knockdown as an additional therapeutic strategy for PCa control.

【 授权许可】

Unknown   
© Ferreira et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.