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https://www.arca.fiocruz.br/handle/icict/13673
PCA3 LONG NONCODING RNA MODULATES THE EXPRESSION OF KEY CANCER-RELATED GENES IN LNCAP PROSTATE CANCER CELLS
Long noncoding RNA
Gene expression
Cancer-related genes
Prostatic Neoplasms
Autor(es)
Afiliação
Fundação Oswaldo Cruz, Bio-Manguinhos, Rio de Janeiro, Brazil
Instituto de Patologia Molecular e Imunologia da Universidade do Porto, Porto, Portugal
Fundação Centro Universitário Estadual da Zona Oeste, Rio de Janeiro, Brazil
Instituto Nacional de Câncer José Alencar Gomes da Silva, Coordenação de Pesquisa, Rio de Janeiro, Brazil
Fundação Oswaldo Cruz, Vice-presidência de Pesquisa e Laboratórios de Referência, Rio de Janeiro, Brazil
Universidade Federal Fluminense, Instituto de Humanidades e Sáude, Departamento de Ciências da Natureza, Rio de Janeiro, Brazil
Instituto de Patologia Molecular e Imunologia da Universidade do Porto, Porto, Portugal
Fundação Centro Universitário Estadual da Zona Oeste, Rio de Janeiro, Brazil
Instituto Nacional de Câncer José Alencar Gomes da Silva, Coordenação de Pesquisa, Rio de Janeiro, Brazil
Fundação Oswaldo Cruz, Vice-presidência de Pesquisa e Laboratórios de Referência, Rio de Janeiro, Brazil
Universidade Federal Fluminense, Instituto de Humanidades e Sáude, Departamento de Ciências da Natureza, Rio de Janeiro, Brazil
Resumo em Inglês
Prostate cancer antigen 3 (PCA3)is a prostate-specific long noncoding RNA (lncRNA) involved in the control of prostate cancer (PCa) cell survival, through modulating androgen receptor (AR) signaling.To furthercomprehendthemechanisms by which PCA3 modulates LNCaP cell survival, we characterized the expression patterns of several cancer-related genes, including those involved in epithelial-mesenchymal transition (EMT) and AR cofactors in response to PCA3 silencing. We also aimed to develop a strategyto stably silence PCA3. SmallinterferingRNA (siRNA) or short hairpinRNA (shRNA) was usedto knock down PCA3inLNCaP cells.The expression of 84cancer-related genes, as well as those coding for AR cofactors and EMT markers, was analyzed by quantitative real-time PCR (qRT-PCR). LNCaPPCA3 silenced cells differentially expressed 16 of the 84 cancer genes tested, mainly those involved in gene expression control and cell signaling. PCA3 knockdown also induced the upregulation of severaltranscripts coding for AR cofactors and modulated the expression of EMT markers. LNCaP cells transduced with lentivirus vectors carrying an shRNA sequence targeting PCA3 stably downregulated PCA3 expression, causing a significant drop (60 %) in the proportion of LNCaP cells expressing the transgene. In conclusion, our data provide evidence that PCA3 silencing modulates the expression of key cancer-related genes, including those coding for AR cofactors and EMT markers. Transducing LNCaP cells with an shRNA sequence targeting PCA3 led to loss of viability of the cells, supporting the proposal of PCA3 knockdown as a putativetherapeutic approachtoinhibit PCa growth.
Palavras-chave em inglês
PCA3Long noncoding RNA
Gene expression
Cancer-related genes
Prostatic Neoplasms
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