Treating metastatic prostate cancer with microRNA-145

Autor(es)

Iscaife, Alexandre ^[1] ; Reis, Sabrina Thalita ^[1] ; Morais, Denis Reis ^[1] ; Viana, Nayara Izabel ^[1] ; da Silva, Iran Amorim ^[1] ; Pimenta, Ruan ^[1] ; Bordini, Andre ^[1] ; Dip, Nelson ^[1] ; Srougi, Miguel ^[1] ; Moreira Leite, Katia Ramos ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med FMUSP, Lab Invest Med, Disciplina Urol LIM 55, Av Dr Arnaldo 455, Sala 2145, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Apoptosis; v. 23, n. 7-8, p. 388-395, AUG 2018.
• Citações Web of Science: 4

Resumo

Prostate cancer (PCa) is an incurable disease at the metastatic stage. Although there are different options for treatment, the results are limited. MicroRNAs (miRNAs) are a group of small, noncoding, regulatory RNAs with important roles in regulating gene expression. miR-145 is reported to be a key tumor suppressor miRNA (tsmiR) that controls important oncogenes, such as MYC and RAS. In this study, in vitro studies were performed to show the control of MYC and RAS by miR-145. Flow cytometry was used to analyze cell proliferation and apoptosis. The efficacy of miR-145 in treating metastatic PCa was tested in nude mice using a model of bone metastasis promoted by intraventricular injection of PC-3MLuc-C6 cells. Tumor growth was evaluated by an in vivo bioluminescence system. After the full establishment of metastases on day 21, six animals were treated with three intravenous doses of miR-145 (on days 21, 24 and 27), and six were injected with scramble miRNA as controls. Compared to the controls, tumor growth was significantly reduced in animals receiving miR-145, most importantly on day 7 after the third and last dose of miRNA. After discontinuing the treatment, tumor growth resumed, becoming similar to the group of non-treated animals. A decrease in MYC and RAS expression was observed in all cell lines after treatment with miR-145, although statistical significance was achieved only in experiments with LNCaP and PC3 cell lines, with a decrease in 56% (p = 0.012) and 31% (p = 0.013) of RAS expression, respectively. Our results suggest that miR-145 is a potential molecule to be tested for treatment of metastatic, castration-resistant PCa. (AU)

• Processo FAPESP: 13/07350-7 - O uso de microRNA para o tratamento do câncer de próstata: estudos in vitro e in vivo
• Beneficiário: Alexandre Iscaife
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 12/21966-8 - O uso de microRNA para o tratamento do câncer de próstata: estudos in vitro e in vivo
• Beneficiário: Kátia Ramos Moreira Leite
• Modalidade de apoio: Auxílio à Pesquisa - Regular