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Merck
CN
  • TRIM59 promotes tumor growth in hepatocellular carcinoma and regulates the cell cycle by degradation of protein phosphatase 1B.

TRIM59 promotes tumor growth in hepatocellular carcinoma and regulates the cell cycle by degradation of protein phosphatase 1B.

Cancer letters (2019-12-26)
Hanning Ying, Lin Ji, Zhiyao Xu, Xiaoxiao Fan, Yifan Tong, Hui Liu, Jia Zhao, Xiujun Cai
摘要

Tripartite motif 59 (TRIM59) is a member of Tripartite motif protein family, which is frequently increased in many human cancers. However, the molecular mechanism of TRIM59 in hepatocellular carcinoma (HCC) has not been fully elucidated. In this study, we report that TRIM59 plays an essential role in growth of HCC. We analyzed RNA sequencing data to explore abnormally expressed TRIM59 in HCC. The effects of TRIM59 on HCC were investigated through in vitro and in vivo assays (i.e., CCK-8 assay, colony formation assay, flow cytometry assay, xenograft model, immunohistochemistry, immunofluorescence and western blot). The mechanism of TRIM59 action was explored through co-immunoprecipitation, immunofluorescence, mass spectrometry and bioinformatics. TRIM59 expression is up-regulated in HCC tissues. A high level of TRIM59 expression is correlated with poor overall and disease-free survival of HCC patients. Knockdown of TRIM59 attenuated proliferation, induced cells arrested at G1/S phase and reduced tumor growth in the mouse xenograft model. Ectopic expression of TRIM59 had the opposite results. Mechanistically, TRIM59 promoted growth and regulated cell cycle. Further studies indicated that TRIM59 might interacted physically with PPM1B, which has been reported to negatively regulate CDKs phosphorylation. We also discovered that TRIM59 increased degradation of PPM1B. TRIM59 overexpression in HCC patients correlated with reduced expression of PPM1B and increased CDKs phosphorylation and cell cycle proteins. Our findings demonstrate that TRIM59 promotes growth by PPM1B/CDKs signaling pathway, indicating a new prognostic biomarker candidate and a potential antitumor target for HCC.

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Millipore
FLAG ® 免疫沉淀试剂盒
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Supelco
GAPDH, standard for protein electrophoresis
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1 mg
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¥8,248.46