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NOP58 induction potentiates chemoresistance of colorectal cancer cells through aerobic glycolysis as evidenced by proteomics analysis

FRONTIERS IN PHARMACOLOGY(2023)

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摘要
Introduction: The majority of individuals diagnosed with advanced colorectal cancer (CRC) will ultimately acquire resistance to 5-FU treatment. An increasing amount of evidence indicates that aerobic glycolysis performs a significant function in the progression and resistance of CRC. Nevertheless, the fundamental mechanisms remain to be fully understood.Methods: Proteomic analysis of 5-FU resistant CRC cells was implemented to identify and determine potential difference expression protein.Results: These proteins may exhibit resistance mechanisms that are potentially linked to the process of aerobic glycolysis. Herein, we found that nucleolar protein 58 (NOP58) has been overexpressed within two 5-FU resistant CRC cells, 116-5FuR and Lovo-5FuR. Meanwhile, the glycolysis rate of drug-resistant cancer cells has increased. NOP58 knockdown decreased glycolysis and enhanced the sensitivity of 116-5FuR and Lovo-5FuR cells to 5FU.Conclusion: The proteomic analysis of chemoresistance identifies a new target involved in the cellular adaption to 5-FU and therefore highlights a possible new therapeutic strategy to overcome this resistance.
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关键词
colorectal cancer,chemoresistance,aerobic glycolysis,5-FU,NOP58
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