title: PCA3 long noncoding RNA modulates the expression of key cancer-related genes in LNCaP prostate cancer cells.
abstract: 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 further comprehend the mechanisms 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 strategy to stably silence PCA3. Small interfering RNA (siRNA) or short hairpin RNA (shRNA) was used to knock down PCA3 in LNCaP cells. The expression of 84 cancer-related genes, as well as those coding for AR cofactors and EMT markers, was analyzed by quantitative real-time PCR (qRT-PCR). LNCaP-PCA3 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 several transcripts 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 putative therapeutic approach to inhibit PCa growth.
authors.affiliation: Fundação Oswaldo Cruz, Bio-Manguinhos, Rio de Janeiro, Brazil.
authors.forename: Ana Emília Goulart
authors.initials: AE
authors.lastname: Lemos
authors.affiliation: Instituto de Patologia Molecular e Imunologia da Universidade do Porto, Porto, Portugal.
authors.forename: Luciana Bueno
authors.initials: LB
authors.lastname: Ferreira
authors.affiliation: Fundação Oswaldo Cruz, Bio-Manguinhos, Rio de Janeiro, Brazil.
authors.forename: Nadia Maria
authors.initials: NM
authors.lastname: Batoreu
authors.affiliation: 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.
authors.forename: Paula Priscilla
authors.initials: PP
authors.lastname: de Freitas
authors.affiliation: 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.
authors.forename: Martin Hernan
authors.initials: MH
authors.lastname: Bonamino
authors.affiliation: Instituto Nacional de Câncer José Alencar Gomes da Silva, Coordenação de Pesquisa, Rio de Janeiro, Brazil. etelgimba@id.uff.br.|Universidade Federal Fluminense, Instituto de Humanidades e Sáude, Departamento de Ciências da Natureza, Rio de Janeiro, Brazil. etelgimba@id.uff.br.
authors.forename: Etel Rodrigues Pereira
authors.initials: ER
authors.lastname: Gimba
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055785:Gene Knockdown Techniques / Q000379:methods; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000951:Antigens, Neoplasm; C479341:prostate cancer antigen 3, human
keywords: Cancer-related genes; Gene expression; Long noncoding RNA; PCA3; Prostate cancer