BUB1B Promotes Proliferation of Prostate Cancer via Transcriptional Regulation of MELK

BACKGROUND: Prostate cancer remains one of both the most common and deadliest forms of cancer, which is still localized generally respond well to radical prostatectomy and associated interventions, up to 30% of these individuals will still suffer from disease relapse. BUB1B has been found to be essential for cell growth and proliferation, even in several kinds of tumor cells. But the specific importance and mechanistic role of BUB1B in prostate cancer remains unclear. METHODS: Quantitative Real-Time PCR and Western-blot were used in detection of mRNA and protein expression. Lentivirus infection was used to overexpression or knock down target gene. Flow cytometry analysis was performed to test protein expression and apoptosis level. Immunohistochemistry was used to identify protein expression in tissue. Statistical differences between two groups are evaluated by two-tailed t-tests. The comparison among multiple groups is performed by one-way Analysis of Variance (ANOVA) followed by Dunnett's posttest. The statistical significance of the Kaplan-Meier survival plot is determined by log-rank analysis. RESULTS: In the present report, we found BUB1B expression to be highly increased in prostate cancer tissues relative to normal controls. We further found BUB1B to be essential for efficient tumor cell proliferation, and to correlate with poorer prostate cancer patient outcomes. From a mechanistic perspective, the ability of BUB1B to regulate MELK was found to be essential for its ability to promote prostate cancer cell proliferation. CONCLUSION: Altogether, our data suggests that BUB1B is up-regulated in prostate cancer, suggesting that growth of cancer cells may depend on BUB1B-dependent regulation of MELK transcription. BUB1B may serve as a clinical prognostic factor and a druggable target for prostate cancer.