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PCL2 regulates p53 stability and functions as a tumor suppressor in breast cancer 被引量:4

PCL2 regulates p53 stability and functions as a tumor suppressor in breast cancer
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摘要 Polycomblike2(PCL2) is a well-known component of polycomb repressive complex 2(PRC2) and plays important roles in H3 K27 methylation and homeotic gene silencing.However,the involvement of PCL2 in breast cancer development remains unclear.Here,we established PCL2 as a tumor suppressor gene in breast cancer.Expression level of PCL2 was significantly downregulated in breast cancer tissue samples observed at different TNM stages.Ectopic expression of PCL2 could significantly inhibit cell proliferation and promoted apoptosis.PCL2 also remarkably elevated levels of p53 and its targets by increasing p53 stability.Mechanistically,PCL2 protected p53 proteins from MDM2-mediated ubiquitination and degradation by sequestering MDM2 into the nucleolus.Overexpression of PCL2 also suppressed migration and invasion by inhibiting epithelial-mesenchymal transition.PCL2 expression was correlated with Ecadherin expression and was inversely correlated with vimentin expression.Furthermore,PCL2 knockdown could attenuate anti-tumor effect of MLN4924.Taken together,our findings indicated that PCL2 played a tumor suppressor role in development and progression of breast cancer and may be a prognostic and predictive marker for breast cancer. Polycomblike2(PCL2) is a well-known component of polycomb repressive complex 2(PRC2) and plays important roles in H3 K27 methylation and homeotic gene silencing.However,the involvement of PCL2 in breast cancer development remains unclear.Here,we established PCL2 as a tumor suppressor gene in breast cancer.Expression level of PCL2 was significantly downregulated in breast cancer tissue samples observed at different TNM stages.Ectopic expression of PCL2 could significantly inhibit cell proliferation and promoted apoptosis.PCL2 also remarkably elevated levels of p53 and its targets by increasing p53 stability.Mechanistically,PCL2 protected p53 proteins from MDM2-mediated ubiquitination and degradation by sequestering MDM2 into the nucleolus.Overexpression of PCL2 also suppressed migration and invasion by inhibiting epithelial-mesenchymal transition.PCL2 expression was correlated with Ecadherin expression and was inversely correlated with vimentin expression.Furthermore,PCL2 knockdown could attenuate anti-tumor effect of MLN4924.Taken together,our findings indicated that PCL2 played a tumor suppressor role in development and progression of breast cancer and may be a prognostic and predictive marker for breast cancer.
出处 《Science Bulletin》 SCIE EI CSCD 2018年第10期629-639,共11页 科学通报(英文版)
基金 supported by the National Key R&D Program of China(2016YFE0129200) the National Natural Science Foundation of China(31571321,31171428) the Institute of the Fundamental Research Funds of Shandong University(2015JC036)
关键词 Polycomb repressive complexes PCL2 p53 MDM2 Breast cancer 肿瘤 p53 稳定性 调整 建筑群 TNM
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