BLM interaction with EZH2 regulates MDM2 expression and is a poor prognostic biomarker for prostate cancer |
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Authors: | Yong Ruan Houqiang Xu Xinqin Ji Jiafu Zhao |
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Affiliation: | 1. Guizhou University School of Medicine, Guiyang, Guizhou, China ; 2. Key Laboratory of Animal Genetics, Breeding and Reproduction in The Plateau Mountainous Region, Ministry of Education, Guiyang, Guizhou, China ; 3. Guizhou Key Laboratory of Animal Heredity, Breeding and Reproduction, Guizhou, China ; 4. College of Animal Science, Guizhou University, Guiyang, Guizhou, China |
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Abstract: | Prostate cancer (PCa) is one of the major causes of cancer death among males worldwide. Our previous studies indicated that the proliferation of prostate cancer cells was reduced after BLM knockdown, however, the mechanism is still not clear. In this study, we identified a direct interaction between BLM and EZH2, which had extremely significantly positive correlations (P<0.001). In vitro, our research revealed that tumor growth was inhibited after EZH2 knockdown and that inhibition could be reversed by BLM overexpression; conversely, tumor growth was promoted after EZH2 overexpression, and promotion could be reversed by BLM knockdown. This suggests that BLM and EZH2 play important roles in the progression of prostate cancer cells. In vivo, the impact of BLM and EZH2 was investigated in mouse xenograft models, and the results showed that EZH2 could be regulated by BLM, which was consistent with our in vitro observations. Our results demonstrated that the expression of P53 is affected by the binding of BLM and EZH2 to the MDM2 promoter region. This finding indicated that EZH2 regulates the expression of MDM2 at the transcriptional level by interacting with BLM. |
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Keywords: | BLM EZH2 prostate cancer prognostic biomarker |
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