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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Apoptosis, Apoptosis Regulatory Proteins, Blotting, Western, Cell Line, Tumor, Cell Proliferation, Computational Biology, Genes, p53, Male, Mice, Mice, Nude, MicroRNAs, Neoplasm Transplantation, Neoplasms, Hormone-Dependent, Prostatic Neoplasms, Tumor Suppressor Proteins, bcl-2 Homologous Antagonist-Killer Protein.
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Does miR-125b promote growth of prostate cancer xenograft tumor through targeting pro-apoptotic genes? Context: Increasing evidence demonstrates that aberrantly regulated microRNAs (miRNAs) contribute to the initiation and progression of human cancer. We previously have demonstrated that miR-125b stimulated the growth of prostate cancer (CaP) cells. In this study, we further determined the influence of miR-125b on the pathogenesis of CaP. To evaluate the effect of miR-125b on xenograft tumor growth, male athymic mice were subcutaneously injected with PC-346C-miR-125b cells that stably overexpressed miR-125b. Potential direct target transcripts of miR-125b were identified using a bioinformatics approach and three miR-125b targeted molecules were confirmed by means of biochemical analyses. Enforced expression of miR-125b promoted tumor growth in both intact and castrated male nude mice. In an effort to define the molecular mechanism(s) mediating its tumor growth properties, we found that miR-125b directly targets eight transcripts, including three key pro-apoptotic genes: p53, Puma, and Bak1. Increasing the abundance of miR-125b resulted in a dramatic decrease in the levels of these three proteins in CaP cells. A direct repressive effect on each of these was supported by the ability of miR-125b to significantly reduce the activity of luciferase reporters containing their 3'-untranslated regions of each gene encompassing the miR-125b-binding sites. Additionally, we found that repression of miR-125b activity was able to sensitize CaP cells to different therapeutic interventions.
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Data obtained in this study demonstrate that miR-125b promotes growth of prostatic xenograft tumors by down-regulating three key pro-apoptotic genes. This suggests that miR-125b is oncogenic and makes it an attractive therapeutic target in CaP. Final Decision: yes