BUB1B Promotes Proliferation of Prostate Cancer via Transcriptional Regulation of MELK

Author(s): Juan-Hua Tian, Li-Jun Mu, Mei-Yu Wang, Jin Zeng, Qing-Zhi Long, Bin Guan, Wen Wang, Yu-Mei Jiang, Xiao-Jing Bai, Yue-Feng Du*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 20 , Issue 9 , 2020


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Abstract:

Background: Prostate cancer remains one of the most common and deadliest forms of cancer, generally respond well to radical prostatectomy and associated interventions, up to 30% of individuals will suffer disease relapse. Although BUB1B was found to be essential for cell growth and proliferation, even in several kinds of tumor cells, the specific importance and mechanistic role of BUB1B in prostate cancer remain unclear.

Methods: Quantitative Real-Time PCR and Western-blot were used in the detection of mRNA and protein expression. Lentivirus infection was used to overexpression or knock down the 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 the 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 suggest that BUB1B is up-regulated in prostate cancer, suggesting that the 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.

Keywords: BUB1B, prostate cancer, MELK, transcriptional regulation, PCR, western-blot.

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Article Details

VOLUME: 20
ISSUE: 9
Year: 2020
Published on: 01 January, 2020
Page: [1140 - 1146]
Pages: 7
DOI: 10.2174/1871520620666200101141934
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