Abstract 2105: miR-125b promotes the tumor growth of prostate cancer cells in intact and castrated male nude mice

Abstract

Abstract Non-coding microRNAs (miRNAs) negatively regulate protein-coding genes, and aberrant expression of certain miRNAs has been reported to play a key role in the pathogenesis of human cancer including prostate cancer. Our previous studies have shown that miR-125b was highly expressed in a majority of clinical prostate cancer tissues we examined and ectopic expression of miR-125b stimulated the in vitro growth of LNCaP cells in the absence of androgens. In this study, we performed in vivo experiments to further determine whether this miRNA promotes prostatic xenograft growth. To this end, a miR-125b lentiviral vector (lenti-miR-125b) that expresses a ∼500-base pre-miR-125b was used to infect androgen-dependent PC-346C prostate cancer cells that have a limited ability to form tumors in intact nude mice and fail to grow in castrated nude mice. Quantitative RT-PCR exhibited a 39-fold increase in miR-125b level in lenti-miR-125b infected cells compared to that in lenti-vector control cells. The effect of miR-125b on xenograft tumor growth was then evaluated in intact and castrated male nude mice. After inoculation with lenti-miR-125b cells or control cells, tumors formed in all intact mice. However, the palpable lenti-miR-125b tumors appeared in approximately 7 days, while the vector control tumors took 15-20 days. The volume of xenograft tumor was markedly enlarged in all lenti-miR-125b mice compared to that in control mice. Surgery castration was performed when the tumor volume reached ∼0.5 cm3. Castratation resulted in temporary growth regression of miR-125b tumors followed by rapid growth of these tumors. To understand the molecular mechanism by which miR-125b promotes tumor growth in intact and castrated nude mice, xenograft tumors were examined by Western blot analyses of the expression of p53, Puma and Bak1 that have been validated to be the direct targets of miR-125b. Marked reduction of these three pro-apoptotic molecules was observed in miR-125b tumors compared to that in control tumors. Our data indicate that miR-125b acts as an oncogenic molecule, and overexpression of miR-125b stimulates the in vivo growth of prostate cancer cells as well as promotes the progression of prostate cancer cells to an androgen-independent status. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2105.